Sibyl Anderson - Academia.edu (original) (raw)

Papers by Sibyl Anderson

Research paper thumbnail of Safety and Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma (HCC) and Child-Pugh A versus B Cirrhosis

Gastrointestinal cancer research : GCR, 2011

We performed a retrospective analysis of data from a phase II study evaluating sorafenib in patie... more We performed a retrospective analysis of data from a phase II study evaluating sorafenib in patients with advanced hepatocellular carcinoma (HCC) to assess differences in safety and efficacy based on Child-Pugh (CP) status (A/B). Patients received sorafenib 400 mg PO bid. We analyzed safety, pharmacokinetic (PK), and efficacy data in the two CP groups. Ninety-eight patients were CP A; 38 were CP B, with a median duration of therapy of 4 and 1.8 months, respectively. Grade 3/4 adverse events in the CP A and B groups, respectively, included hyperbilirubinemia (14% and 53%), ascites (3% and 5%), and encephalopathy (3% and 13%). Median overall survival (OS) in the CP A group was 9.5 months, compared with 3.2 months in the CP B population. Responses were limited in both groups. AUC and C(max) values were comparable between the two groups. Due to the lack of randomization against placebo or no therapy in this study, it is unclear if the more frequent worsening of liver cirrhosis and outco...

Research paper thumbnail of Factors Associated with Adherence Rates for Oral and Intravenous Anticancer Therapy in Commercially Insured Patients with Metastatic Colon Cancer

Journal of Managed Care & Specialty Pharmacy, 2016

Over the past decade, oncology therapies have trended toward orally administered regimens, and th... more Over the past decade, oncology therapies have trended toward orally administered regimens, and there has been growing attention on evaluation of factors that affect adherence. There has not been a rigorous investigation of factors associated with adherence to intravenous (IV) and oral anticancer drugs in the setting of metastatic colorectal cancer (mCRC). To (a) assess potential patient-specific factors related to adherence to mCRC chemotherapy regimens and (b) compare adherence with IV versus oral dosage forms. A retrospective analysis was performed using the Optum Oncology Management claims database. Patients aged 18 years and older diagnosed with mCRC between July 1, 2004, and December 31, 2010, who were insured by a commercial health plan were included in the study. Adherence to IV and oral chemotherapy regimens was assessed using the National Comprehensive Cancer Network (NCCN) guidelines as the standard for expected cycle/regimen duration. The most commonly prescribed chemotherapy regimens were assessed. Adherence was evaluated using the medication possession ratio (MPR), calculated as the number of days a patient was covered by their chemotherapy regimen, according to NCCN guidelines, divided by the number of days elapsed from the first to the last infusion of that regimen. For most analyses, the MPR was considered a continuous variable that could take on values between 0 and 1. In other analyses, a dichotomous categorical variable designated if the MPR was at least 0.8 versus less than 0.8. The Wilcoxon rank sum, Kruskal-Wallis, and Student's t-test were used to detect differences in continuous measures between patients receiving oral capecitabine therapy versus IV chemotherapy. The chi square test (X(2) test) or Fisher's exact test was used to assess differences in the dichotomous MPR variable. Generalized estimating equation (GEE) models were used for regimen-level analyses to account for correlated responses within individuals. A total of 6,780 patients were included in the analysis, virtually all (98%) with commercial insurance coverage and the remaining (2%) with Medicare Advantage. Patients with mCRC received 17,095 regimens of chemotherapy, including 2,252 regimens of oral capecitabine. Of the 17,095 regimens, 6,780 (40%) were first-line regimens (i.e., the first time mCRC was treated for a given patient). The most common chemotherapy regimen, regardless of line of therapy, was FOLFOX (2,991 regimens, 17.5% of all regimens used). FOLFOX-based therapies with or without bevacizumab were the most common regimens for first- and second-line chemotherapy, while oral capecitabine treatment was the most commonly prescribed regimen for patients in third- or fourth-line therapy. Overall, medication adherence across all regimens was relatively high, with a mean MPR of 0.87 (SD = 0.17). Evaluation of the distribution of IV and oral capecitabine regimens revealed that 28% of all regimens were associated with an MPR of less than 0.8. The average MPR was clinically similar, but statistically higher for IV chemotherapy regimens (0.881) compared with oral capecitabine regimens (0.799; P < 0.0001). In the multivariable GEE model, lung or liver metastases were associated with a higher MPR, while lower Charlson Comorbidity Index and oral anticancer therapy were associated with lower MPR. Furthermore, as line of therapy increased, the difference in MPR between patients receiving oral capecitabine and IV chemotherapy increased. This analysis determined that adherence with IV chemotherapy regimens was clinically similar, but statistically higher, compared to oral capecitabine therapy. The difference in adherence rates between the 2 routes of administration increased as the line of anticancer regimen increased. These results suggest that there should be an increased focus on improving adherence rates in patients receiving oral capecitabine. This study was funded by Bayer HealthCare Pharmaceuticals. At the time of this study, Seal was an employee with Bayer HealthCare Pharmaceuticals; Anderson is employed by Bayer HealthCare Pharmaceuticals. Study concept and design were contributed by Seal and Shermock. Seal was responsible for data acquisition. Data analysis was conducted by Shermock. Interpretation of analyses was conducted by Shermock, Seal, and Anderson. The manuscript was written by Shermock, and all authors shared equally in revisions and final approval of the submitted manuscript.

Research paper thumbnail of Phase II Trial of 96-Hour Paclitaxel in Previously Treated Patients with Advanced Esophageal Cancer: ORIGINAL ARTICLE

Cancer Investigation, Feb 1, 2003

A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lun... more A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lung cancer and breast cancer refractory to short-duration infusion paclitaxel. Given the activity of paclitaxel in esophageal cancer, a phase II trial of 96-hour infusion paclitaxel in esophageal cancer was undertaken. Both adenocarcinoma and squamous cell histology were included. Paclitaxel was administered at 140 mg/m2 over 96 hours every 21 days. Patients who had metastatic disease to the liver and transaminases greater than two times normal value received 120 mg/m2. Response to treatment was evaluated after the first two cycles and subsequently every third cycle. Ten men and four women were entered. All were eligible for response and had stage IV disease. Thirteen patients were previously treated. All 13 received prior short-duration paclitaxel-containing chemotherapy regimens. Eleven patients had adenocarcinoma and three squamous cell cancer. Patients completed a mean of two cycles (range one to eight) prior to disease progression. No major responses were observed. Toxicity was minimal and included grade 3/4 neutropenia in 14% of patients. One patient with adenocarcinoma demonstrated stable disease for 28 weeks. No major activity was observed in a population of previously treated patients. Ninety-six-hour paclitaxel in metastatic esophageal cancer is generally well tolerated with minimal toxicity; however, it is ineffective in previously treated patients. Further evaluation of this schedule of paclitaxel in combination with concurrent radiotherapy, where its radiosensitizing potential may be useful, is ongoing in locally advanced esophageal cancer.

Research paper thumbnail of Combined modality chemoradiation in elderly oesophageal cancer patients

British journal of cancer, Jan 18, 2007

We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the pr... more We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66-88) with a diagnosis of stage II-III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3-4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months...

Research paper thumbnail of Combined modality therapy in esophageal cancer: The Memorial experience

Seminars in Surgical Oncology, 2003

Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of i... more Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an aggressive disease, and poor survival is achieved with surgery or chemoradiation therapy alone. Ongoing trials are investigating the use of preoperative chemoradiation followed by surgical resection. Chemoradiation employing a combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is the most commonly used therapy. The significant gastrointestinal toxicity of traditional cisplatin/5-FU-based regimens has prompted the evaluation of new agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center has conducted chemoradiation trials with weekly paclitaxel/cisplatin and irinotecan/cisplatin, and the results suggest that this regimen has the potential to improve the therapeutic index without compromising efficacy. Randomized trials are now being conducted to evaluate the tolerance and efficacy of paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with radiotherapy in locally advanced esophageal cancer. The incorporation of these non-5-FU-based therapies with novel biologic agents is planned.

Research paper thumbnail of Topotecan and liposomal doxorubicin in recurrent ovarian cancer: is sequence important?

International Journal of Gynecological Cancer, 2006

Dupont J, Aghajanian C, Andrea G, Lovegren M, Chuai S, Venkatraman E, Hensley M, Anderson S, Spri... more Dupont J, Aghajanian C, Andrea G, Lovegren M, Chuai S, Venkatraman E, Hensley M, Anderson S, Spriggs D, Sabbatini P. Topotecan and liposomal doxorubicin in recurrent ovarian cancer: is sequence important? Int J Gynecol Cancer 2006;16(Suppl. 1):68-73.

Research paper thumbnail of Phase II Trial of 96-Hour Paclitaxel in Previously Treated Patients with Advanced Esophageal Cancer

Cancer Investigation, 2003

A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lun... more A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lung cancer and breast cancer refractory to short-duration infusion paclitaxel. Given the activity of paclitaxel in esophageal cancer, a phase II trial of 96-hour infusion paclitaxel in esophageal cancer was undertaken. Both adenocarcinoma and squamous cell histology were included. Paclitaxel was administered at 140 mg/m2 over 96 hours every 21 days. Patients who had metastatic disease to the liver and transaminases greater than two times normal value received 120 mg/m2. Response to treatment was evaluated after the first two cycles and subsequently every third cycle. Ten men and four women were entered. All were eligible for response and had stage IV disease. Thirteen patients were previously treated. All 13 received prior short-duration paclitaxel-containing chemotherapy regimens. Eleven patients had adenocarcinoma and three squamous cell cancer. Patients completed a mean of two cycles (range one to eight) prior to disease progression. No major responses were observed. Toxicity was minimal and included grade 3/4 neutropenia in 14% of patients. One patient with adenocarcinoma demonstrated stable disease for 28 weeks. No major activity was observed in a population of previously treated patients. Ninety-six-hour paclitaxel in metastatic esophageal cancer is generally well tolerated with minimal toxicity; however, it is ineffective in previously treated patients. Further evaluation of this schedule of paclitaxel in combination with concurrent radiotherapy, where its radiosensitizing potential may be useful, is ongoing in locally advanced esophageal cancer.

Research paper thumbnail of A retrospective analysis of vinorelbine chemotherapy for patients with previously treated soft-tissue sarcomas

Sarcoma, 2006

Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We pre... more Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We present retrospective single institution experience with single-agent vinorelbine in subjects with metastatic soft tissue malignancies. Methods. Fifty-eight patients were treated with single agent intravenous vinorelbine between April 1997 and December 2004. Doxorubicin had been administered previously to 53 subjects (91%), and the median number of lines of previous chemotherapy was 3 (range 0-7). Results. Patients received a median 6 doses of vinorelbine (range 1-65). The overall response rate was 6% (3 patients: 1 angiosarcoma, 1 epithelioid sarcoma, and 1 embryonal rhabdomyosarcoma). Fourteen patients (26%) experienced a best result of stable disease. Median time to progression was 1.8 months (95% confidence intervals 1.5-2.1 months, Kaplan-Meier estimate). Eight patients experienced grade 3 or 4 toxicity, most commonly febrile neutropenia. Conclusion. Vinorelbine demonstrates limited ac...

Research paper thumbnail of Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma

Cancer, Jan 15, 2004

Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowled... more Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowledge, little is known regarding the hormonal expression patterns of leiomyosarcomas (LMSs) of the uterus. The objective of the current study was to assess the immunohistochemical (IHC) patterns of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) expression in LMA and LMS of the uterus using a tissue microarray. The authors also sought to assess the prognostic value of ER, PR, and AR expression in LMS. Between January 1991 and March 2001, 25 patients were identified with primary uterine LMS for whom tissue was available. A tissue microarray was created with 3 representative cores from each of the LMS cases, as well as from 19 cases with benign uterine LMA. IHC staining was scored as follows: negative (0-1) and positive (2-3). Outcome analyses were performed for LMS only. First recurrence was determined from the time of the initial diagnosis. Survival was determ...

Research paper thumbnail of Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single-agent carboplatin originally treated with carboplatin and paclitaxel. The Memorial Sloan-Kettering Cancer Center experience

Gynecologic oncology, 2003

There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no cur... more There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no curative options, many oncologists choose to treat women who recur with carboplatin, particularly if they are deemed to have platinum-sensitive disease. However, particularly in the era of platinum-taxane treatment as primary therapy, the utility of this treatment has not been established, nor is it clear whether the results of single-agent treatment are equivalent to that of combination therapy. We sought to determine the outcomes for patients with platinum-sensitive EOC who were treated with carboplatin-taxane therapy and received single-agent carboplatin (C) as second chemotherapy. In addition, we sought to compare these results to the outcomes in women who received carboplatin and paclitaxel (C + T) at first relapse. We identified 24 patients using our electronic institutional database with a histologically confirmed diagnosis of ovarian cancer that had a complete response to platinum-p...

Research paper thumbnail of Sorafenib for Older Patients With Renal Cell Carcinoma: Subset Analysis From a Randomized Trial

JNCI Journal of the National Cancer Institute, 2008

Research paper thumbnail of Detection of K-ras Oncogene Mutations in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

JNCI Journal of the National Cancer Institute, 1995

Research paper thumbnail of Early Detection and Prognosis of Ovarian Cancer Using Serum YKL-40

Journal of Clinical Oncology, 2004

YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer ... more YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer serum markers, CA125 and CA15-3, for the detection of early-stage ovarian cancer.

Research paper thumbnail of Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial

Journal of Clinical Oncology, 2009

Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic ... more Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported. Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated. The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib. Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.

Research paper thumbnail of Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas

Journal of Clinical Oncology, 2005

To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients wi... more To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

Research paper thumbnail of Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study

International Journal of Gynecological Cancer, 2007

in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J ... more in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J Gynecol Cancer 2007;17:197-203.

Research paper thumbnail of P53, Epidermal Growth Factor, and Platelet-Derived Growth Factor in Uterine Leiomyosarcoma and Leiomyomas

International Journal of Gynecological Cancer, 2006

Uterine leiomyosarcoma (ULMS) is an aggressive gynecological disease. Although ULMS are often fou... more Uterine leiomyosarcoma (ULMS) is an aggressive gynecological disease. Although ULMS are often found in association with benign leiomyoma (LMA), little is known regarding the relationship between these benign and malignant smooth muscle neoplasms. The objective of this study was to evaluate the expression of epidermal growth factor (EGFR), platelet-derived growth factor (PDGFR), and p53 in ULMS specimens, their prognostic relevance, and the expression of these molecular markers when compared to benign LMA specimens. Between 1991 and 2001, 25 patients were identified with high-grade primary ULMS and for whom tissue was available. Tissue microarray was created with three representative cores from each of the ULMS cases as well as from 19 patients with benign uterine leiomyomata. Immunohistochemical (IHC) staining was performed for EGFR, PDGFR, and p53. Negative and positive IHC staining was scored for each marker. Outcome analysis was performed only for ULMS. Survival was determined from the time of initial diagnosis to last follow-up. Twelve (48%) ULMS expressed p53 compared to none of the LMA (P < 0.001), and 15 (60%) ULMS cases showed PDGFR expression compared to 32% of LMA samples (P= 0.08). EGFR expression did not differ between ULMS and LMA groups. ULMS patients with p53 expression had a poorer survival compared to ULMS patients with negative expression (P= 0.07). ULMS tumor stage had the strongest association with overall survival (P= 0.05). Our study supports previous investigations indicating that p53 expression may serve as a prognostic marker for ULMS patients. The difference in PDGFR expression between ULMS and LMA demonstrated a trend toward significance. EGFR was not commonly expressed in ULMS. These uniquely expressed markers may assist in stratifying patients by survival and identify novel therapeutic markers. Clearly, further investigation is needed.

Research paper thumbnail of Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single-agent carboplatin originally treated with carboplatin and paclitaxel

Gynecologic Oncology, 2003

Objective. There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there... more Objective. There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no curative options, many oncologists choose to treat women who recur with carboplatin, particularly if they are deemed to have platinum-sensitive disease. However, particularly in the era of platinum-taxane treatment as primary therapy, the utility of this treatment has not been established, nor is it clear whether the results of single-agent treatment are equivalent to that of combination therapy. We sought to determine the outcomes for patients with platinum-sensitive EOC who were treated with carboplatin-taxane therapy and received single-agent carboplatin (C) as second chemotherapy. In addition, we sought to compare these results to the outcomes in women who received carboplatin and paclitaxel (C ϩ T) at first relapse.

Research paper thumbnail of Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma

Gynecologic Oncology, 2006

The primary aim of this study was to investigate the expression of apoptotic and cell cycle regul... more The primary aim of this study was to investigate the expression of apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine leiomyosarcoma in order to identify molecular pathways that possibly could be important in the development of leiomyosarcoma. A secondary aim was to examine if the apoptotic and cell cycle regulatory protein expression profile of uterine leiomyosarcoma is potentially useful for clinical prognostic purposes. A tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine leiomyomas was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53 using standard techniques. Staining was scored 0-12 for each marker, 0-3 being negative and 4-12 positive. Outcome analyses were performed only for leiomyosarcomas. First recurrence was determined from the time of initial diagnosis. Survival was determined from the time of initial diagnosis to last follow-up. Associations were found between disease type (leiomyosarcoma vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54% vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a univariate analysis. In a multivariate analysis, tumor stage was the only independent significant prognostic factor (P = 0.002). The significant differential expression of apoptotic and cell cycle regulatory proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors suggests that pathways involving these proteins may be important in the development of malignant disease and, therefore, could be potential targets for molecular therapies.

Research paper thumbnail of Temozolomide in uterine leiomyosarcomas

Gynecologic Oncology, 2005

Objective. Temozolomide has been studied in soft-tissue sarcomas with varying dosing schedules. W... more Objective. Temozolomide has been studied in soft-tissue sarcomas with varying dosing schedules. We review the Memorial Sloan-Kettering Cancer Center (MSKCC) experience in women with metastatic or unresectable leiomyosarcoma treated with continuous daily dose (CDD) or bolus-dose (BD) temozolomide. We include a literature review of temozolomide activity in leiomyosarcoma patients.

Research paper thumbnail of Safety and Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma (HCC) and Child-Pugh A versus B Cirrhosis

Gastrointestinal cancer research : GCR, 2011

We performed a retrospective analysis of data from a phase II study evaluating sorafenib in patie... more We performed a retrospective analysis of data from a phase II study evaluating sorafenib in patients with advanced hepatocellular carcinoma (HCC) to assess differences in safety and efficacy based on Child-Pugh (CP) status (A/B). Patients received sorafenib 400 mg PO bid. We analyzed safety, pharmacokinetic (PK), and efficacy data in the two CP groups. Ninety-eight patients were CP A; 38 were CP B, with a median duration of therapy of 4 and 1.8 months, respectively. Grade 3/4 adverse events in the CP A and B groups, respectively, included hyperbilirubinemia (14% and 53%), ascites (3% and 5%), and encephalopathy (3% and 13%). Median overall survival (OS) in the CP A group was 9.5 months, compared with 3.2 months in the CP B population. Responses were limited in both groups. AUC and C(max) values were comparable between the two groups. Due to the lack of randomization against placebo or no therapy in this study, it is unclear if the more frequent worsening of liver cirrhosis and outco...

Research paper thumbnail of Factors Associated with Adherence Rates for Oral and Intravenous Anticancer Therapy in Commercially Insured Patients with Metastatic Colon Cancer

Journal of Managed Care & Specialty Pharmacy, 2016

Over the past decade, oncology therapies have trended toward orally administered regimens, and th... more Over the past decade, oncology therapies have trended toward orally administered regimens, and there has been growing attention on evaluation of factors that affect adherence. There has not been a rigorous investigation of factors associated with adherence to intravenous (IV) and oral anticancer drugs in the setting of metastatic colorectal cancer (mCRC). To (a) assess potential patient-specific factors related to adherence to mCRC chemotherapy regimens and (b) compare adherence with IV versus oral dosage forms. A retrospective analysis was performed using the Optum Oncology Management claims database. Patients aged 18 years and older diagnosed with mCRC between July 1, 2004, and December 31, 2010, who were insured by a commercial health plan were included in the study. Adherence to IV and oral chemotherapy regimens was assessed using the National Comprehensive Cancer Network (NCCN) guidelines as the standard for expected cycle/regimen duration. The most commonly prescribed chemotherapy regimens were assessed. Adherence was evaluated using the medication possession ratio (MPR), calculated as the number of days a patient was covered by their chemotherapy regimen, according to NCCN guidelines, divided by the number of days elapsed from the first to the last infusion of that regimen. For most analyses, the MPR was considered a continuous variable that could take on values between 0 and 1. In other analyses, a dichotomous categorical variable designated if the MPR was at least 0.8 versus less than 0.8. The Wilcoxon rank sum, Kruskal-Wallis, and Student's t-test were used to detect differences in continuous measures between patients receiving oral capecitabine therapy versus IV chemotherapy. The chi square test (X(2) test) or Fisher's exact test was used to assess differences in the dichotomous MPR variable. Generalized estimating equation (GEE) models were used for regimen-level analyses to account for correlated responses within individuals. A total of 6,780 patients were included in the analysis, virtually all (98%) with commercial insurance coverage and the remaining (2%) with Medicare Advantage. Patients with mCRC received 17,095 regimens of chemotherapy, including 2,252 regimens of oral capecitabine. Of the 17,095 regimens, 6,780 (40%) were first-line regimens (i.e., the first time mCRC was treated for a given patient). The most common chemotherapy regimen, regardless of line of therapy, was FOLFOX (2,991 regimens, 17.5% of all regimens used). FOLFOX-based therapies with or without bevacizumab were the most common regimens for first- and second-line chemotherapy, while oral capecitabine treatment was the most commonly prescribed regimen for patients in third- or fourth-line therapy. Overall, medication adherence across all regimens was relatively high, with a mean MPR of 0.87 (SD = 0.17). Evaluation of the distribution of IV and oral capecitabine regimens revealed that 28% of all regimens were associated with an MPR of less than 0.8. The average MPR was clinically similar, but statistically higher for IV chemotherapy regimens (0.881) compared with oral capecitabine regimens (0.799; P < 0.0001). In the multivariable GEE model, lung or liver metastases were associated with a higher MPR, while lower Charlson Comorbidity Index and oral anticancer therapy were associated with lower MPR. Furthermore, as line of therapy increased, the difference in MPR between patients receiving oral capecitabine and IV chemotherapy increased. This analysis determined that adherence with IV chemotherapy regimens was clinically similar, but statistically higher, compared to oral capecitabine therapy. The difference in adherence rates between the 2 routes of administration increased as the line of anticancer regimen increased. These results suggest that there should be an increased focus on improving adherence rates in patients receiving oral capecitabine. This study was funded by Bayer HealthCare Pharmaceuticals. At the time of this study, Seal was an employee with Bayer HealthCare Pharmaceuticals; Anderson is employed by Bayer HealthCare Pharmaceuticals. Study concept and design were contributed by Seal and Shermock. Seal was responsible for data acquisition. Data analysis was conducted by Shermock. Interpretation of analyses was conducted by Shermock, Seal, and Anderson. The manuscript was written by Shermock, and all authors shared equally in revisions and final approval of the submitted manuscript.

Research paper thumbnail of Phase II Trial of 96-Hour Paclitaxel in Previously Treated Patients with Advanced Esophageal Cancer: ORIGINAL ARTICLE

Cancer Investigation, Feb 1, 2003

A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lun... more A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lung cancer and breast cancer refractory to short-duration infusion paclitaxel. Given the activity of paclitaxel in esophageal cancer, a phase II trial of 96-hour infusion paclitaxel in esophageal cancer was undertaken. Both adenocarcinoma and squamous cell histology were included. Paclitaxel was administered at 140 mg/m2 over 96 hours every 21 days. Patients who had metastatic disease to the liver and transaminases greater than two times normal value received 120 mg/m2. Response to treatment was evaluated after the first two cycles and subsequently every third cycle. Ten men and four women were entered. All were eligible for response and had stage IV disease. Thirteen patients were previously treated. All 13 received prior short-duration paclitaxel-containing chemotherapy regimens. Eleven patients had adenocarcinoma and three squamous cell cancer. Patients completed a mean of two cycles (range one to eight) prior to disease progression. No major responses were observed. Toxicity was minimal and included grade 3/4 neutropenia in 14% of patients. One patient with adenocarcinoma demonstrated stable disease for 28 weeks. No major activity was observed in a population of previously treated patients. Ninety-six-hour paclitaxel in metastatic esophageal cancer is generally well tolerated with minimal toxicity; however, it is ineffective in previously treated patients. Further evaluation of this schedule of paclitaxel in combination with concurrent radiotherapy, where its radiosensitizing potential may be useful, is ongoing in locally advanced esophageal cancer.

Research paper thumbnail of Combined modality chemoradiation in elderly oesophageal cancer patients

British journal of cancer, Jan 18, 2007

We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the pr... more We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66-88) with a diagnosis of stage II-III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3-4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months...

Research paper thumbnail of Combined modality therapy in esophageal cancer: The Memorial experience

Seminars in Surgical Oncology, 2003

Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of i... more Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an aggressive disease, and poor survival is achieved with surgery or chemoradiation therapy alone. Ongoing trials are investigating the use of preoperative chemoradiation followed by surgical resection. Chemoradiation employing a combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is the most commonly used therapy. The significant gastrointestinal toxicity of traditional cisplatin/5-FU-based regimens has prompted the evaluation of new agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center has conducted chemoradiation trials with weekly paclitaxel/cisplatin and irinotecan/cisplatin, and the results suggest that this regimen has the potential to improve the therapeutic index without compromising efficacy. Randomized trials are now being conducted to evaluate the tolerance and efficacy of paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with radiotherapy in locally advanced esophageal cancer. The incorporation of these non-5-FU-based therapies with novel biologic agents is planned.

Research paper thumbnail of Topotecan and liposomal doxorubicin in recurrent ovarian cancer: is sequence important?

International Journal of Gynecological Cancer, 2006

Dupont J, Aghajanian C, Andrea G, Lovegren M, Chuai S, Venkatraman E, Hensley M, Anderson S, Spri... more Dupont J, Aghajanian C, Andrea G, Lovegren M, Chuai S, Venkatraman E, Hensley M, Anderson S, Spriggs D, Sabbatini P. Topotecan and liposomal doxorubicin in recurrent ovarian cancer: is sequence important? Int J Gynecol Cancer 2006;16(Suppl. 1):68-73.

Research paper thumbnail of Phase II Trial of 96-Hour Paclitaxel in Previously Treated Patients with Advanced Esophageal Cancer

Cancer Investigation, 2003

A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lun... more A 96-hour infusion schedule of paclitaxel demonstrates tolerability and antitumor activity in lung cancer and breast cancer refractory to short-duration infusion paclitaxel. Given the activity of paclitaxel in esophageal cancer, a phase II trial of 96-hour infusion paclitaxel in esophageal cancer was undertaken. Both adenocarcinoma and squamous cell histology were included. Paclitaxel was administered at 140 mg/m2 over 96 hours every 21 days. Patients who had metastatic disease to the liver and transaminases greater than two times normal value received 120 mg/m2. Response to treatment was evaluated after the first two cycles and subsequently every third cycle. Ten men and four women were entered. All were eligible for response and had stage IV disease. Thirteen patients were previously treated. All 13 received prior short-duration paclitaxel-containing chemotherapy regimens. Eleven patients had adenocarcinoma and three squamous cell cancer. Patients completed a mean of two cycles (range one to eight) prior to disease progression. No major responses were observed. Toxicity was minimal and included grade 3/4 neutropenia in 14% of patients. One patient with adenocarcinoma demonstrated stable disease for 28 weeks. No major activity was observed in a population of previously treated patients. Ninety-six-hour paclitaxel in metastatic esophageal cancer is generally well tolerated with minimal toxicity; however, it is ineffective in previously treated patients. Further evaluation of this schedule of paclitaxel in combination with concurrent radiotherapy, where its radiosensitizing potential may be useful, is ongoing in locally advanced esophageal cancer.

Research paper thumbnail of A retrospective analysis of vinorelbine chemotherapy for patients with previously treated soft-tissue sarcomas

Sarcoma, 2006

Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We pre... more Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We present retrospective single institution experience with single-agent vinorelbine in subjects with metastatic soft tissue malignancies. Methods. Fifty-eight patients were treated with single agent intravenous vinorelbine between April 1997 and December 2004. Doxorubicin had been administered previously to 53 subjects (91%), and the median number of lines of previous chemotherapy was 3 (range 0-7). Results. Patients received a median 6 doses of vinorelbine (range 1-65). The overall response rate was 6% (3 patients: 1 angiosarcoma, 1 epithelioid sarcoma, and 1 embryonal rhabdomyosarcoma). Fourteen patients (26%) experienced a best result of stable disease. Median time to progression was 1.8 months (95% confidence intervals 1.5-2.1 months, Kaplan-Meier estimate). Eight patients experienced grade 3 or 4 toxicity, most commonly febrile neutropenia. Conclusion. Vinorelbine demonstrates limited ac...

Research paper thumbnail of Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma

Cancer, Jan 15, 2004

Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowled... more Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowledge, little is known regarding the hormonal expression patterns of leiomyosarcomas (LMSs) of the uterus. The objective of the current study was to assess the immunohistochemical (IHC) patterns of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) expression in LMA and LMS of the uterus using a tissue microarray. The authors also sought to assess the prognostic value of ER, PR, and AR expression in LMS. Between January 1991 and March 2001, 25 patients were identified with primary uterine LMS for whom tissue was available. A tissue microarray was created with 3 representative cores from each of the LMS cases, as well as from 19 cases with benign uterine LMA. IHC staining was scored as follows: negative (0-1) and positive (2-3). Outcome analyses were performed for LMS only. First recurrence was determined from the time of the initial diagnosis. Survival was determ...

Research paper thumbnail of Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single-agent carboplatin originally treated with carboplatin and paclitaxel. The Memorial Sloan-Kettering Cancer Center experience

Gynecologic oncology, 2003

There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no cur... more There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no curative options, many oncologists choose to treat women who recur with carboplatin, particularly if they are deemed to have platinum-sensitive disease. However, particularly in the era of platinum-taxane treatment as primary therapy, the utility of this treatment has not been established, nor is it clear whether the results of single-agent treatment are equivalent to that of combination therapy. We sought to determine the outcomes for patients with platinum-sensitive EOC who were treated with carboplatin-taxane therapy and received single-agent carboplatin (C) as second chemotherapy. In addition, we sought to compare these results to the outcomes in women who received carboplatin and paclitaxel (C + T) at first relapse. We identified 24 patients using our electronic institutional database with a histologically confirmed diagnosis of ovarian cancer that had a complete response to platinum-p...

Research paper thumbnail of Sorafenib for Older Patients With Renal Cell Carcinoma: Subset Analysis From a Randomized Trial

JNCI Journal of the National Cancer Institute, 2008

Research paper thumbnail of Detection of K-ras Oncogene Mutations in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

JNCI Journal of the National Cancer Institute, 1995

Research paper thumbnail of Early Detection and Prognosis of Ovarian Cancer Using Serum YKL-40

Journal of Clinical Oncology, 2004

YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer ... more YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer serum markers, CA125 and CA15-3, for the detection of early-stage ovarian cancer.

Research paper thumbnail of Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial

Journal of Clinical Oncology, 2009

Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic ... more Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported. Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated. The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib. Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.

Research paper thumbnail of Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas

Journal of Clinical Oncology, 2005

To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients wi... more To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

Research paper thumbnail of Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study

International Journal of Gynecological Cancer, 2007

in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J ... more in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J Gynecol Cancer 2007;17:197-203.

Research paper thumbnail of P53, Epidermal Growth Factor, and Platelet-Derived Growth Factor in Uterine Leiomyosarcoma and Leiomyomas

International Journal of Gynecological Cancer, 2006

Uterine leiomyosarcoma (ULMS) is an aggressive gynecological disease. Although ULMS are often fou... more Uterine leiomyosarcoma (ULMS) is an aggressive gynecological disease. Although ULMS are often found in association with benign leiomyoma (LMA), little is known regarding the relationship between these benign and malignant smooth muscle neoplasms. The objective of this study was to evaluate the expression of epidermal growth factor (EGFR), platelet-derived growth factor (PDGFR), and p53 in ULMS specimens, their prognostic relevance, and the expression of these molecular markers when compared to benign LMA specimens. Between 1991 and 2001, 25 patients were identified with high-grade primary ULMS and for whom tissue was available. Tissue microarray was created with three representative cores from each of the ULMS cases as well as from 19 patients with benign uterine leiomyomata. Immunohistochemical (IHC) staining was performed for EGFR, PDGFR, and p53. Negative and positive IHC staining was scored for each marker. Outcome analysis was performed only for ULMS. Survival was determined from the time of initial diagnosis to last follow-up. Twelve (48%) ULMS expressed p53 compared to none of the LMA (P < 0.001), and 15 (60%) ULMS cases showed PDGFR expression compared to 32% of LMA samples (P= 0.08). EGFR expression did not differ between ULMS and LMA groups. ULMS patients with p53 expression had a poorer survival compared to ULMS patients with negative expression (P= 0.07). ULMS tumor stage had the strongest association with overall survival (P= 0.05). Our study supports previous investigations indicating that p53 expression may serve as a prognostic marker for ULMS patients. The difference in PDGFR expression between ULMS and LMA demonstrated a trend toward significance. EGFR was not commonly expressed in ULMS. These uniquely expressed markers may assist in stratifying patients by survival and identify novel therapeutic markers. Clearly, further investigation is needed.

Research paper thumbnail of Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single-agent carboplatin originally treated with carboplatin and paclitaxel

Gynecologic Oncology, 2003

Objective. There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there... more Objective. There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no curative options, many oncologists choose to treat women who recur with carboplatin, particularly if they are deemed to have platinum-sensitive disease. However, particularly in the era of platinum-taxane treatment as primary therapy, the utility of this treatment has not been established, nor is it clear whether the results of single-agent treatment are equivalent to that of combination therapy. We sought to determine the outcomes for patients with platinum-sensitive EOC who were treated with carboplatin-taxane therapy and received single-agent carboplatin (C) as second chemotherapy. In addition, we sought to compare these results to the outcomes in women who received carboplatin and paclitaxel (C ϩ T) at first relapse.

Research paper thumbnail of Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma

Gynecologic Oncology, 2006

The primary aim of this study was to investigate the expression of apoptotic and cell cycle regul... more The primary aim of this study was to investigate the expression of apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine leiomyosarcoma in order to identify molecular pathways that possibly could be important in the development of leiomyosarcoma. A secondary aim was to examine if the apoptotic and cell cycle regulatory protein expression profile of uterine leiomyosarcoma is potentially useful for clinical prognostic purposes. A tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine leiomyomas was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53 using standard techniques. Staining was scored 0-12 for each marker, 0-3 being negative and 4-12 positive. Outcome analyses were performed only for leiomyosarcomas. First recurrence was determined from the time of initial diagnosis. Survival was determined from the time of initial diagnosis to last follow-up. Associations were found between disease type (leiomyosarcoma vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54% vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a univariate analysis. In a multivariate analysis, tumor stage was the only independent significant prognostic factor (P = 0.002). The significant differential expression of apoptotic and cell cycle regulatory proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors suggests that pathways involving these proteins may be important in the development of malignant disease and, therefore, could be potential targets for molecular therapies.

Research paper thumbnail of Temozolomide in uterine leiomyosarcomas

Gynecologic Oncology, 2005

Objective. Temozolomide has been studied in soft-tissue sarcomas with varying dosing schedules. W... more Objective. Temozolomide has been studied in soft-tissue sarcomas with varying dosing schedules. We review the Memorial Sloan-Kettering Cancer Center (MSKCC) experience in women with metastatic or unresectable leiomyosarcoma treated with continuous daily dose (CDD) or bolus-dose (BD) temozolomide. We include a literature review of temozolomide activity in leiomyosarcoma patients.