Kishan Pandya | University of Rochester (original) (raw)

Papers by Kishan Pandya

American Journal of Clinical Oncology, 1989

We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced ... more We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced and refractory prostate carcinoma. All the patients had failed at least one endocrine therapy. Six patients received only one prior hormonal treatment. Five patients were off study within 3 weeks due to early death and toxicity, 14 had progressive disease, and 9 had stable disease. No objective partial remission was observed, but the nine stable patients had therapeutic benefit, with improvement in bone pain and performance status for a median duration of 153 days. Three patients withdrew because of postural hypotension, dizziness, weakness, and lethargy. The median survival of the entire group was 186 days (range 41-606 days). Our results suggest that aminoglutethemide and hydrocortisone can be an alternative treatment for patients with advanced and refractory prostate carcinoma.

Cancer, 1986

The authors have studied five cases of biopsy-proven pulmonary toxicity caused by the administrat... more The authors have studied five cases of biopsy-proven pulmonary toxicity caused by the administration of mitomycin C (M), vincristine, and cisplatin in 64 patients with advanced non-small cell lung cancer. The clinical triad of progressive dyspnea, rales, and pulmonary infiltrates presented in all five cases. In addition, pulmonary function tests showed hypoxemia (four/five), reduced forced vital capacity (three/four), total lung capacity (two/three), and forced expiratory volume (FEV1) (three/four) and very profound reduction in diffusion capacity (three/three). Transbronchial biopsy for tissue examination was necessary to rule out other causes. Characteristics but nonspecific pathologic changes were documented in all five cases. All the patients responded quickly and dramatically to high-dose glucocorticoids with improvement of hypoxia, dyspnea, exercise tolerance, and sense of well being. In three patients the pulmonary infiltrates cleared. However, abrupt stopping or early withdrawal of steroid resulted in aggravation of dyspnea and pulmonary infiltrate in three cases who improved subsequently with escalation of steroid doses. The authors conclude that the treatment of choice for pulmonary toxicity induced by M or M-containing chemotherapy regimens is a high dose of glucocorticoid and discontinuation of M at once when suspicion is raised.

American Journal of Clinical Oncology, 1998

Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional... more Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.

Cancer, 1986

The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 pati... more The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 patients with advanced non-small cell lung cancer (NSCLC) were evaluated for their potential synergistic cytotoxicity. The overall response rate was 43% (27/63); in the 54 eligible and evaluable patients, the response rate was 50% (27/54). Responses were observed in all cell types and disease sites. Cell type; performance status of 0, 1, or 2; sex; and age younger or older than 60 years did not significantly influence the response rate. However, patients with prior radiation had significantly more treatment failure than those without. The dose-limiting side effects in these 54 patients were myelosuppression (40%), pulmonary fibrosis (9%), peripheral neuropathy (6%), and intractable nausea and vomiting (4%). The degree of leukopenia (P less than 0.01) but not of thrombocytopenia increased significantly in patients who had received prior radiotherapy. One patient died of marked thrombocytopenia and one of fulminant hepatitis. Patients who responded lived significantly longer than those who did not (P less than 0.004). A majority of the responders (82%) also achieved symptomatic palliation. With appropriate dose modification and supportive care, MVP was tolerable. Further trials with this regimen or a modified version are worth consideration.

American Journal of Clinical Oncology, 1986

Twenty-three patients with advanced colorectal carcinoma, mostly with liver and lung metastases a... more Twenty-three patients with advanced colorectal carcinoma, mostly with liver and lung metastases and measurable disease, were treated with mitomycin-C 20 mg/m2 I.V. and vincristine 1.2 mg/m2 I.V. every 6 weeks, and cisplatinum 50 mg/m2 I.V. and 5-fluorouracil 1,000 mg/m2/24 hours I.V. continuous infusion for 96 hours every 3 weeks based upon the hypothesis that cisplatinum may potentiate the antitumor activity of antimetabolites and alkylating agents. Five patients had received prior chemotherapy and six had received prior radiotherapy, with one of these patients receiving both. One complete and 10 partial responses were observed, with an overall response rate of 48% (90% confidence interval 30-70%). The toxicity was manageable. A possible potentiating effect of cisplatinum is suggested in this first attempt in the treatment of colorectal cancer, and warrants further exploration.

American Journal of Clinical Oncology, 1989

Ten patients with metastatic breast cancer refractory to multiple chemotherapeutic regimens as we... more Ten patients with metastatic breast cancer refractory to multiple chemotherapeutic regimens as well as hormonal therapy were treated with continuous intravenous infusion of 5-fluorouracil (5-FU) at 200-300 mg/m2/24 h through a Broviac catheter using a Cormed pump. The treatment was continued until toxicity developed and restarted after resolution of the toxicity. Most common dose-limiting toxicities were mucositis and diarrhea. No grade II or worse myelosuppression was documented. All the patients had received 5-FU by bolus injection before entering the study. We observed three partial responses and one improvement, with two patients continued on the study (396+ and 90+ days, respectively). We conclude that continuous infusion of 5-FU is safe and tolerable even by heavily pretreated patients with poor performance status and is not cross-resistant to bolus injection of 5-FU and other chemotherapeutic agents. Our report warrants further investigation.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2003

A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignanc... more A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignancy was conducted. The study was based on preclinical research of the effects of paclitaxel on apoptosis and the cell cycle in human cancer cell lines. Three human epithelial cancer cell lines were investigated for preclinical study. Cells were analyzed for apoptosis and cell cycle characteristics after paclitaxel treatment. The Phase I/II clinical trial for non-small cell lung cancer used pulsed low-dose paclitaxel three times/week with the starting dose of 15 mg/m(2). Daily thoracic radiotherapy was delivered in 1.8 Gy/fraction to 60-65 Gy for gross disease and to 45-58 Gy for microscopic disease. Timing of radiotherapy was delayed to allow for a minimum of 4 h for cell cycle progression. Forty-one patients have enrolled and 33 completed treatments. Seventeen patients completed the Phase I study, with an average primary tumor shrinkage of 83 +/- 8% (95% confidence interval). Tumor respon...

Toxicology letters, 1982

The toxic effects of i.p. administered n-hexane and n-heptane on biochemical processes in rat liv... more The toxic effects of i.p. administered n-hexane and n-heptane on biochemical processes in rat liver, as indicated by the increase in alkaline phosphatase activity and decrease in FDP aldolase activity, and their reflection on blood chemistry, were studied. Serum cholinesterase activity and albumin and cholesterol content showed statistically significant decreases with the increase in FDP aldolase activity. The significance of the findings is discussed.

American Journal of Clinical Oncology-cancer Clinical Trials, 1989

We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced ... more We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced and refractory prostate carcinoma. All the patients had failed at least one endocrine therapy. Six patients received only one prior hormonal treatment. Five patients were off study within 3 weeks due to early death and toxicity, 14 had progressive disease, and 9 had stable disease. No objective partial remission was observed, but the nine stable patients had therapeutic benefit, with improvement in bone pain and performance status for a median duration of 153 days. Three patients withdrew because of postural hypotension, dizziness, weakness, and lethargy. The median survival of the entire group was 186 days (range 41-606 days). Our results suggest that aminoglutethemide and hydrocortisone can be an alternative treatment for patients with advanced and refractory prostate carcinoma.

Toxicology Letters, 1989

The effect of oral administration of trichloroethylene, a neurotoxic solvent, on the levels of ph... more The effect of oral administration of trichloroethylene, a neurotoxic solvent, on the levels of phosphoinositides in rat brain was studied. Two hours after administration of a single dose of trichloroethylene (1000 mg/kg body wt.), the levels of phosphatidylinositol (PI) and phosphatidylinositol 4,5-biphosphate (PIP2) were reduced by 24 and 17%, respectively, without any significant change in that of phosphatidylinositol-4-phosphate (PIP). Twenty hours after treatment, the levels of PI and PIP2 were increased by 22 and 38%, respectively. Repeated administration of the same dose of trichloroethylene for 1 year markedly reduced the levels of PI (52%), PIP (23%) and PIP2 (45%). These results for the first time suggest the involvement of a phosphoinositide messenger system in trichloroethylene neurotoxicity.

Oncology, 2004

To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vi... more To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil (MVPF) in patients with metastatic large bowel cancer. A total of 94 patients with no prior chemotherapy and measurable metastatic large bowel cancer were randomly assigned to one of the two treatment regimens. Eastern Cooperative Oncology Group (ECOG) criteria were used to evaluate response and toxicity. Fifty patients were randomized to PF and 44 to MVPF. Toxicity was evaluable in all patients except one; response was evaluable in 40 and 31, with response rate of 13 and 42%, respectively. Intent-to-treat analysis showed a response rate of 12 and 32%, respectively (p = 0.076), where it was assumed that none of the ineligible or unevaluable patients responded. Median survival for all patients was 9 months, with no difference between PF and MVPF. ECOG Performance Status (0 vs. 1), weight loss (< or =10 vs. >10%) and site of metastatic lesion had statistically significant impact on survival. MVPF was definitely more toxic than PF (p < 0.000005). Both treatment regimens showed clinical activity. The MVPF regimen resulted in more responses than PF, no improvement in survival, and more toxicity.

Oncology Nursing Forum, 2010

To determine the feasibility of administering a flavonoid-rich adjunctive treatment (Concord grap... more To determine the feasibility of administering a flavonoid-rich adjunctive treatment (Concord grape juice) for the management of chemotherapy-induced nausea and vomiting (CINV); to evaluate the usefulness of existing measures for assessing CINV frequency and severity, quality of life, control over life events, and psychological state; to identify any actual or potential adverse events associated with frequent grape juice intake; and to provide preliminary data concerning the effect of Concord grape juice on CINV, quality of life, perceived control over life events, and psychological state. Double-blind, randomized clinical trial. A cancer center in an academic health science center in the northeastern United States. 77 adult patients with cancer receiving moderately or highly emetogenic chemotherapy agents. Participants drank 4 oz. of grape juice or placebo prior to meals for one week following each of four chemotherapy treatment cycles. They recorded frequency, duration, and distress of nausea, vomiting, and retching daily, beginning the evening of chemotherapy administration and continuing for seven days. Data were analyzed with generalized estimating equations methodology to model differences between groups over time. Nausea and vomiting frequency, duration, and distress; quality of life; control over decision making; and psychological state. Nausea and vomiting frequency, duration, and distress were lower for experimental group members, although a high attrition rate (50%) resulted in insufficient power to detect statistically significant differences over time. Greater levels of anxiety, depression, and hostility at baseline were related to nausea and vomiting, quality of life, and perceived control over decision making. The effect of grape juice flavonoids on CINV should be investigated further with a larger sample to determine whether preliminary findings are supported. Alterations to the study protocol will be necessary to decrease attrition. Flavonoid-rich fruits and vegetables may provide additional protection against CINV. If the compounds work, they would offer a low-cost, readily available adjunctive treatment for the management of CINV.

New England Journal of Medicine, 1994

Pain is often inadequately treated in patients with cancer. A total of 1308 outpatients with meta... more Pain is often inadequately treated in patients with cancer. A total of 1308 outpatients with metastatic cancer from 54 treatment locations affiliated with the Eastern Cooperative Oncology Group rated the severity of their pain during the preceding week, as well as the degree of pain-related functional impairment and the degree of relief provided by analgesic drugs. Their physicians attributed the pain to various factors, described its treatment, and estimated the impact of pain on the patients' ability to function. We assessed the adequacy of prescribed analgesic drugs using guidelines developed by the World Health Organization, studied the factors that influenced whether analgesia was adequate, and determined the effects of inadequate analgesia on the patients' perception of pain relief and functional status. Sixty-seven percent of the patients (871 of 1308) reported that they had had pain or had taken analgesic drugs daily during the week preceding the study, and 36 percent (475 of 1308) had pain severe enough to impair their ability to function. Forty-two percent of those with pain (250 of the 597 patients for whom we had complete information) were not given adequate analgesic therapy. Patients seen at centers that treated predominantly minorities were three times more likely than those treated elsewhere to have inadequate pain management. A discrepancy between patient and physician in judging the severity of the patient's pain was predictive of inadequate pain management (odds ratio, 2.3). Other factors that predicted inadequate pain management included pain that physicians did not attribute to cancer (odds ratio, 1.9), better performance status (odds ratio, 1.8), age of 70 years or older (odds ratio, 2.4), and female sex (odds ratio, 1.5). Patients with less adequate analgesia reported less pain relief and greater pain-related impairment of function. Despite published guidelines for pain management, many patients with cancer have considerable pain and receive inadequate analgesia.

Lung Cancer, 2010

This study was designed to evaluate the efficacy and safety of combined zoledronic acid and docet... more This study was designed to evaluate the efficacy and safety of combined zoledronic acid and docetaxel/carboplatin in patients with non-small cell lung cancer (NSCLC) as preclinical studies showed synergistic antitumoral activity with bisphosphonates and docetaxel. Patients with inoperable stage IIIB or stage IV NSCLC were randomized 2:1 to receive docetaxel 75mg/m(2) and carboplatin area under the concentration time curve 6 with (Arm A) or without (Arm B) zoledronic acid 4mg every 3 weeks for 6 cycles. Patients responding in Arm A were rerandomized to receive monthly zoledronic acid (maximum: 12 months [Arm A1] or no zoledronic acid [Arm A2]). Patients responding in Arm B entered Arm B1 for follow-up evaluation only. The primary endpoint was the proportion of patients without disease progression; secondary endpoints were time to disease progression (TTP), TTP in bone, best overall response rate, 1-year overall survival (OS) time, and safety; study not powered to detect endpoint differences. Of 150 patients, 98 were randomized to Arm A and 52 to Arm B. In the treatment phase, results were similar between groups in the proportion of patients without disease progression (40.9% vs 38.8%; P=.8096) and median TTP (132d vs 132d; P=.9622). One-year OS times and best overall response rates were 266d vs 206d (P=.4855) and 64.1% vs 72% (P=.3423), respectively; the study was not powered to detect differences. In the follow-up phase, TTP and OS time were similar. Adding zoledronic acid to docetaxel/carboplatin in advanced stage NSCLC patients was well tolerated, but provided little to no effect on disease progression endpoints.

The Lancet, 2005

Background Most women receiving systemic therapy for breast cancer experience hot flashes. We und... more Background Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer.

Journal of Thoracic Oncology, 2007

To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimu... more To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimus (CCI-779) after induction chemotherapy in patients with extensive small-cell lung cancer. Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan were randomized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression. Eighty-seven patients entered between January 2002 and December 2003, of whom 85 were eligible: 44 received 25 mg (arm A), and 41 received 250 mg (arm B). The overall median follow-up time for all eligible patients was 34.6 months. Median age was 59 years (range, 39-80); 42 (49.4%) were male and 43 (50.6%) female; 12.9% had brain metastases. The overall median and 1-year PFS were 2.2 months (95% confidence interval [CI]: 1.8, 2.9) and 4.7% (95% CI: 0.2%, 9.2%), respectively. The median PFS (95% CI) for arm A was 1.9 months (1.6, 2.3); for arm B, it was 2.5 months (1.9, 3.4; p = 0.24). The median overall survival from randomization was 8 months (95% CI: 6.5, 9.5). Among the 86 patients with reported toxicities, 36 (42%) had grade 3 toxicities, the most common of which were thrombocytopenia, hypophosphatemia, and fatigue, and an additional 12 (14%) had grade 4 toxicities, the most common of which was neutropenia. No patients experienced lethal toxicities. Temsirolimus (CCI 779), given at 25 or 250 mg weekly, seemed not to increase the PFS in this patient population.

Journal of Thoracic Oncology, 2008

Poor local disease control remains a major obstacle for inoperable non-small cell lung cancer (NS... more Poor local disease control remains a major obstacle for inoperable non-small cell lung cancer (NSCLC) after radiotherapy. We previously reported results of a phase I/II clinical study based on preclinical investigations of paclitaxel radiation interactions for inoperable locally advanced NSCLC, which yielded remarkable local tumor responses and durable in-field tumor control using schedule-dependent low-dose paclitaxel for radiosensitization. Given our unique results, we analyzed the tumor response kinetics and conducted a statistical modeling of tumor response to characterize this regimen. A total of 104 chest CT scans from 27 patients treated in the clinical trial were evaluated. Tumor volumes were calculated by three-dimensional measurements of pretreatment and serial post-therapy CT scans. A nonlinear mixed effects model was used to model response kinetics. The average tumor volume reduction at 1 month post-therapy was 69.9 +/- 22.6% (standard deviation), and was 80.6 +/- 17.9% at the last follow-up. The nonlinear mixed effects model predicts that tumor volume will ultimately shrink by at least 75% for more than 75% of patients treated by this regimen. The model also suggests that maximum shrinkage is reached within 2 months after treatment. Tumor volume response kinetics revealed a rapid shrinkage of gross tumors using schedule-dependent pulsed low-dose paclitaxel radiosensitization. This is contrary to the protracted tumor regression process observed in radiation alone or other chemoradiation combinations. Statistical modeling may prove useful in characterizing and comparing different therapeutic regimens.

Journal of Thoracic Oncology, 2008

Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (N... more Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis. Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79-6.18), median survival was 10.1 month (95% CI: 5.95-14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%). Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.

Journal of Pain and Symptom Management, 2009

Recent guidelines developed by the U.S. Food and Drug Administration for the use of patientreport... more Recent guidelines developed by the U.S. Food and Drug Administration for the use of patientreported outcomes discuss the rating of pain and other symptoms at their current level of severity versus rating these symptoms using a recall period, such as the past 24 hours or past week. To explore whether the overall experience of cancer patients is better represented by ratings of current pain or by pain recalled from the past week, we conducted a secondary analysis of Eastern Cooperative Oncology Group data from 1,147 cancer patients who had reported having persistent pain during the past week. Patients used the Brief Pain Inventory (BPI) to rate their current pain along with their pain at its worst, least, and average during the past week. T-tests were used to compare ratings of current pain and pain recalled from the past week. Linear regressions described the extent to which the various pain ratings contributed to overall pain interference, also derived from the BPI. Overall, patients rated their current pain as less severe than their worst or average pain recalled from the past week. Worst pain recalled from the past week contributed most to ratings of pain interference. These findings indicate that ratings of recalled worst pain, rather than ratings of current pain, might better reflect the overall experience of pain and its impact on function in cancer patients with persistent pain. Our results provide information that might guide the choice of recall period for cancer clinical trials with pain as a self-reported outcome.

American Journal of Clinical Oncology, 1989

We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced ... more We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced and refractory prostate carcinoma. All the patients had failed at least one endocrine therapy. Six patients received only one prior hormonal treatment. Five patients were off study within 3 weeks due to early death and toxicity, 14 had progressive disease, and 9 had stable disease. No objective partial remission was observed, but the nine stable patients had therapeutic benefit, with improvement in bone pain and performance status for a median duration of 153 days. Three patients withdrew because of postural hypotension, dizziness, weakness, and lethargy. The median survival of the entire group was 186 days (range 41-606 days). Our results suggest that aminoglutethemide and hydrocortisone can be an alternative treatment for patients with advanced and refractory prostate carcinoma.

Cancer, 1986

The authors have studied five cases of biopsy-proven pulmonary toxicity caused by the administrat... more The authors have studied five cases of biopsy-proven pulmonary toxicity caused by the administration of mitomycin C (M), vincristine, and cisplatin in 64 patients with advanced non-small cell lung cancer. The clinical triad of progressive dyspnea, rales, and pulmonary infiltrates presented in all five cases. In addition, pulmonary function tests showed hypoxemia (four/five), reduced forced vital capacity (three/four), total lung capacity (two/three), and forced expiratory volume (FEV1) (three/four) and very profound reduction in diffusion capacity (three/three). Transbronchial biopsy for tissue examination was necessary to rule out other causes. Characteristics but nonspecific pathologic changes were documented in all five cases. All the patients responded quickly and dramatically to high-dose glucocorticoids with improvement of hypoxia, dyspnea, exercise tolerance, and sense of well being. In three patients the pulmonary infiltrates cleared. However, abrupt stopping or early withdrawal of steroid resulted in aggravation of dyspnea and pulmonary infiltrate in three cases who improved subsequently with escalation of steroid doses. The authors conclude that the treatment of choice for pulmonary toxicity induced by M or M-containing chemotherapy regimens is a high dose of glucocorticoid and discontinuation of M at once when suspicion is raised.

American Journal of Clinical Oncology, 1998

Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional... more Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.

Cancer, 1986

The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 pati... more The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 patients with advanced non-small cell lung cancer (NSCLC) were evaluated for their potential synergistic cytotoxicity. The overall response rate was 43% (27/63); in the 54 eligible and evaluable patients, the response rate was 50% (27/54). Responses were observed in all cell types and disease sites. Cell type; performance status of 0, 1, or 2; sex; and age younger or older than 60 years did not significantly influence the response rate. However, patients with prior radiation had significantly more treatment failure than those without. The dose-limiting side effects in these 54 patients were myelosuppression (40%), pulmonary fibrosis (9%), peripheral neuropathy (6%), and intractable nausea and vomiting (4%). The degree of leukopenia (P less than 0.01) but not of thrombocytopenia increased significantly in patients who had received prior radiotherapy. One patient died of marked thrombocytopenia and one of fulminant hepatitis. Patients who responded lived significantly longer than those who did not (P less than 0.004). A majority of the responders (82%) also achieved symptomatic palliation. With appropriate dose modification and supportive care, MVP was tolerable. Further trials with this regimen or a modified version are worth consideration.

American Journal of Clinical Oncology, 1986

Twenty-three patients with advanced colorectal carcinoma, mostly with liver and lung metastases a... more Twenty-three patients with advanced colorectal carcinoma, mostly with liver and lung metastases and measurable disease, were treated with mitomycin-C 20 mg/m2 I.V. and vincristine 1.2 mg/m2 I.V. every 6 weeks, and cisplatinum 50 mg/m2 I.V. and 5-fluorouracil 1,000 mg/m2/24 hours I.V. continuous infusion for 96 hours every 3 weeks based upon the hypothesis that cisplatinum may potentiate the antitumor activity of antimetabolites and alkylating agents. Five patients had received prior chemotherapy and six had received prior radiotherapy, with one of these patients receiving both. One complete and 10 partial responses were observed, with an overall response rate of 48% (90% confidence interval 30-70%). The toxicity was manageable. A possible potentiating effect of cisplatinum is suggested in this first attempt in the treatment of colorectal cancer, and warrants further exploration.

American Journal of Clinical Oncology, 1989

Ten patients with metastatic breast cancer refractory to multiple chemotherapeutic regimens as we... more Ten patients with metastatic breast cancer refractory to multiple chemotherapeutic regimens as well as hormonal therapy were treated with continuous intravenous infusion of 5-fluorouracil (5-FU) at 200-300 mg/m2/24 h through a Broviac catheter using a Cormed pump. The treatment was continued until toxicity developed and restarted after resolution of the toxicity. Most common dose-limiting toxicities were mucositis and diarrhea. No grade II or worse myelosuppression was documented. All the patients had received 5-FU by bolus injection before entering the study. We observed three partial responses and one improvement, with two patients continued on the study (396+ and 90+ days, respectively). We conclude that continuous infusion of 5-FU is safe and tolerable even by heavily pretreated patients with poor performance status and is not cross-resistant to bolus injection of 5-FU and other chemotherapeutic agents. Our report warrants further investigation.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2003

A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignanc... more A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignancy was conducted. The study was based on preclinical research of the effects of paclitaxel on apoptosis and the cell cycle in human cancer cell lines. Three human epithelial cancer cell lines were investigated for preclinical study. Cells were analyzed for apoptosis and cell cycle characteristics after paclitaxel treatment. The Phase I/II clinical trial for non-small cell lung cancer used pulsed low-dose paclitaxel three times/week with the starting dose of 15 mg/m(2). Daily thoracic radiotherapy was delivered in 1.8 Gy/fraction to 60-65 Gy for gross disease and to 45-58 Gy for microscopic disease. Timing of radiotherapy was delayed to allow for a minimum of 4 h for cell cycle progression. Forty-one patients have enrolled and 33 completed treatments. Seventeen patients completed the Phase I study, with an average primary tumor shrinkage of 83 +/- 8% (95% confidence interval). Tumor respon...

Toxicology letters, 1982

The toxic effects of i.p. administered n-hexane and n-heptane on biochemical processes in rat liv... more The toxic effects of i.p. administered n-hexane and n-heptane on biochemical processes in rat liver, as indicated by the increase in alkaline phosphatase activity and decrease in FDP aldolase activity, and their reflection on blood chemistry, were studied. Serum cholinesterase activity and albumin and cholesterol content showed statistically significant decreases with the increase in FDP aldolase activity. The significance of the findings is discussed.

American Journal of Clinical Oncology-cancer Clinical Trials, 1989

We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced ... more We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced and refractory prostate carcinoma. All the patients had failed at least one endocrine therapy. Six patients received only one prior hormonal treatment. Five patients were off study within 3 weeks due to early death and toxicity, 14 had progressive disease, and 9 had stable disease. No objective partial remission was observed, but the nine stable patients had therapeutic benefit, with improvement in bone pain and performance status for a median duration of 153 days. Three patients withdrew because of postural hypotension, dizziness, weakness, and lethargy. The median survival of the entire group was 186 days (range 41-606 days). Our results suggest that aminoglutethemide and hydrocortisone can be an alternative treatment for patients with advanced and refractory prostate carcinoma.

Toxicology Letters, 1989

The effect of oral administration of trichloroethylene, a neurotoxic solvent, on the levels of ph... more The effect of oral administration of trichloroethylene, a neurotoxic solvent, on the levels of phosphoinositides in rat brain was studied. Two hours after administration of a single dose of trichloroethylene (1000 mg/kg body wt.), the levels of phosphatidylinositol (PI) and phosphatidylinositol 4,5-biphosphate (PIP2) were reduced by 24 and 17%, respectively, without any significant change in that of phosphatidylinositol-4-phosphate (PIP). Twenty hours after treatment, the levels of PI and PIP2 were increased by 22 and 38%, respectively. Repeated administration of the same dose of trichloroethylene for 1 year markedly reduced the levels of PI (52%), PIP (23%) and PIP2 (45%). These results for the first time suggest the involvement of a phosphoinositide messenger system in trichloroethylene neurotoxicity.

Oncology, 2004

To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vi... more To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil (MVPF) in patients with metastatic large bowel cancer. A total of 94 patients with no prior chemotherapy and measurable metastatic large bowel cancer were randomly assigned to one of the two treatment regimens. Eastern Cooperative Oncology Group (ECOG) criteria were used to evaluate response and toxicity. Fifty patients were randomized to PF and 44 to MVPF. Toxicity was evaluable in all patients except one; response was evaluable in 40 and 31, with response rate of 13 and 42%, respectively. Intent-to-treat analysis showed a response rate of 12 and 32%, respectively (p = 0.076), where it was assumed that none of the ineligible or unevaluable patients responded. Median survival for all patients was 9 months, with no difference between PF and MVPF. ECOG Performance Status (0 vs. 1), weight loss (< or =10 vs. >10%) and site of metastatic lesion had statistically significant impact on survival. MVPF was definitely more toxic than PF (p < 0.000005). Both treatment regimens showed clinical activity. The MVPF regimen resulted in more responses than PF, no improvement in survival, and more toxicity.

Oncology Nursing Forum, 2010

To determine the feasibility of administering a flavonoid-rich adjunctive treatment (Concord grap... more To determine the feasibility of administering a flavonoid-rich adjunctive treatment (Concord grape juice) for the management of chemotherapy-induced nausea and vomiting (CINV); to evaluate the usefulness of existing measures for assessing CINV frequency and severity, quality of life, control over life events, and psychological state; to identify any actual or potential adverse events associated with frequent grape juice intake; and to provide preliminary data concerning the effect of Concord grape juice on CINV, quality of life, perceived control over life events, and psychological state. Double-blind, randomized clinical trial. A cancer center in an academic health science center in the northeastern United States. 77 adult patients with cancer receiving moderately or highly emetogenic chemotherapy agents. Participants drank 4 oz. of grape juice or placebo prior to meals for one week following each of four chemotherapy treatment cycles. They recorded frequency, duration, and distress of nausea, vomiting, and retching daily, beginning the evening of chemotherapy administration and continuing for seven days. Data were analyzed with generalized estimating equations methodology to model differences between groups over time. Nausea and vomiting frequency, duration, and distress; quality of life; control over decision making; and psychological state. Nausea and vomiting frequency, duration, and distress were lower for experimental group members, although a high attrition rate (50%) resulted in insufficient power to detect statistically significant differences over time. Greater levels of anxiety, depression, and hostility at baseline were related to nausea and vomiting, quality of life, and perceived control over decision making. The effect of grape juice flavonoids on CINV should be investigated further with a larger sample to determine whether preliminary findings are supported. Alterations to the study protocol will be necessary to decrease attrition. Flavonoid-rich fruits and vegetables may provide additional protection against CINV. If the compounds work, they would offer a low-cost, readily available adjunctive treatment for the management of CINV.

New England Journal of Medicine, 1994

Pain is often inadequately treated in patients with cancer. A total of 1308 outpatients with meta... more Pain is often inadequately treated in patients with cancer. A total of 1308 outpatients with metastatic cancer from 54 treatment locations affiliated with the Eastern Cooperative Oncology Group rated the severity of their pain during the preceding week, as well as the degree of pain-related functional impairment and the degree of relief provided by analgesic drugs. Their physicians attributed the pain to various factors, described its treatment, and estimated the impact of pain on the patients' ability to function. We assessed the adequacy of prescribed analgesic drugs using guidelines developed by the World Health Organization, studied the factors that influenced whether analgesia was adequate, and determined the effects of inadequate analgesia on the patients' perception of pain relief and functional status. Sixty-seven percent of the patients (871 of 1308) reported that they had had pain or had taken analgesic drugs daily during the week preceding the study, and 36 percent (475 of 1308) had pain severe enough to impair their ability to function. Forty-two percent of those with pain (250 of the 597 patients for whom we had complete information) were not given adequate analgesic therapy. Patients seen at centers that treated predominantly minorities were three times more likely than those treated elsewhere to have inadequate pain management. A discrepancy between patient and physician in judging the severity of the patient's pain was predictive of inadequate pain management (odds ratio, 2.3). Other factors that predicted inadequate pain management included pain that physicians did not attribute to cancer (odds ratio, 1.9), better performance status (odds ratio, 1.8), age of 70 years or older (odds ratio, 2.4), and female sex (odds ratio, 1.5). Patients with less adequate analgesia reported less pain relief and greater pain-related impairment of function. Despite published guidelines for pain management, many patients with cancer have considerable pain and receive inadequate analgesia.

Lung Cancer, 2010

This study was designed to evaluate the efficacy and safety of combined zoledronic acid and docet... more This study was designed to evaluate the efficacy and safety of combined zoledronic acid and docetaxel/carboplatin in patients with non-small cell lung cancer (NSCLC) as preclinical studies showed synergistic antitumoral activity with bisphosphonates and docetaxel. Patients with inoperable stage IIIB or stage IV NSCLC were randomized 2:1 to receive docetaxel 75mg/m(2) and carboplatin area under the concentration time curve 6 with (Arm A) or without (Arm B) zoledronic acid 4mg every 3 weeks for 6 cycles. Patients responding in Arm A were rerandomized to receive monthly zoledronic acid (maximum: 12 months [Arm A1] or no zoledronic acid [Arm A2]). Patients responding in Arm B entered Arm B1 for follow-up evaluation only. The primary endpoint was the proportion of patients without disease progression; secondary endpoints were time to disease progression (TTP), TTP in bone, best overall response rate, 1-year overall survival (OS) time, and safety; study not powered to detect endpoint differences. Of 150 patients, 98 were randomized to Arm A and 52 to Arm B. In the treatment phase, results were similar between groups in the proportion of patients without disease progression (40.9% vs 38.8%; P=.8096) and median TTP (132d vs 132d; P=.9622). One-year OS times and best overall response rates were 266d vs 206d (P=.4855) and 64.1% vs 72% (P=.3423), respectively; the study was not powered to detect differences. In the follow-up phase, TTP and OS time were similar. Adding zoledronic acid to docetaxel/carboplatin in advanced stage NSCLC patients was well tolerated, but provided little to no effect on disease progression endpoints.

The Lancet, 2005

Background Most women receiving systemic therapy for breast cancer experience hot flashes. We und... more Background Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer.

Journal of Thoracic Oncology, 2007

To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimu... more To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimus (CCI-779) after induction chemotherapy in patients with extensive small-cell lung cancer. Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan were randomized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression. Eighty-seven patients entered between January 2002 and December 2003, of whom 85 were eligible: 44 received 25 mg (arm A), and 41 received 250 mg (arm B). The overall median follow-up time for all eligible patients was 34.6 months. Median age was 59 years (range, 39-80); 42 (49.4%) were male and 43 (50.6%) female; 12.9% had brain metastases. The overall median and 1-year PFS were 2.2 months (95% confidence interval [CI]: 1.8, 2.9) and 4.7% (95% CI: 0.2%, 9.2%), respectively. The median PFS (95% CI) for arm A was 1.9 months (1.6, 2.3); for arm B, it was 2.5 months (1.9, 3.4; p = 0.24). The median overall survival from randomization was 8 months (95% CI: 6.5, 9.5). Among the 86 patients with reported toxicities, 36 (42%) had grade 3 toxicities, the most common of which were thrombocytopenia, hypophosphatemia, and fatigue, and an additional 12 (14%) had grade 4 toxicities, the most common of which was neutropenia. No patients experienced lethal toxicities. Temsirolimus (CCI 779), given at 25 or 250 mg weekly, seemed not to increase the PFS in this patient population.

Journal of Thoracic Oncology, 2008

Poor local disease control remains a major obstacle for inoperable non-small cell lung cancer (NS... more Poor local disease control remains a major obstacle for inoperable non-small cell lung cancer (NSCLC) after radiotherapy. We previously reported results of a phase I/II clinical study based on preclinical investigations of paclitaxel radiation interactions for inoperable locally advanced NSCLC, which yielded remarkable local tumor responses and durable in-field tumor control using schedule-dependent low-dose paclitaxel for radiosensitization. Given our unique results, we analyzed the tumor response kinetics and conducted a statistical modeling of tumor response to characterize this regimen. A total of 104 chest CT scans from 27 patients treated in the clinical trial were evaluated. Tumor volumes were calculated by three-dimensional measurements of pretreatment and serial post-therapy CT scans. A nonlinear mixed effects model was used to model response kinetics. The average tumor volume reduction at 1 month post-therapy was 69.9 +/- 22.6% (standard deviation), and was 80.6 +/- 17.9% at the last follow-up. The nonlinear mixed effects model predicts that tumor volume will ultimately shrink by at least 75% for more than 75% of patients treated by this regimen. The model also suggests that maximum shrinkage is reached within 2 months after treatment. Tumor volume response kinetics revealed a rapid shrinkage of gross tumors using schedule-dependent pulsed low-dose paclitaxel radiosensitization. This is contrary to the protracted tumor regression process observed in radiation alone or other chemoradiation combinations. Statistical modeling may prove useful in characterizing and comparing different therapeutic regimens.

Journal of Thoracic Oncology, 2008

Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (N... more Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis. Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79-6.18), median survival was 10.1 month (95% CI: 5.95-14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%). Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.

Journal of Pain and Symptom Management, 2009

Recent guidelines developed by the U.S. Food and Drug Administration for the use of patientreport... more Recent guidelines developed by the U.S. Food and Drug Administration for the use of patientreported outcomes discuss the rating of pain and other symptoms at their current level of severity versus rating these symptoms using a recall period, such as the past 24 hours or past week. To explore whether the overall experience of cancer patients is better represented by ratings of current pain or by pain recalled from the past week, we conducted a secondary analysis of Eastern Cooperative Oncology Group data from 1,147 cancer patients who had reported having persistent pain during the past week. Patients used the Brief Pain Inventory (BPI) to rate their current pain along with their pain at its worst, least, and average during the past week. T-tests were used to compare ratings of current pain and pain recalled from the past week. Linear regressions described the extent to which the various pain ratings contributed to overall pain interference, also derived from the BPI. Overall, patients rated their current pain as less severe than their worst or average pain recalled from the past week. Worst pain recalled from the past week contributed most to ratings of pain interference. These findings indicate that ratings of recalled worst pain, rather than ratings of current pain, might better reflect the overall experience of pain and its impact on function in cancer patients with persistent pain. Our results provide information that might guide the choice of recall period for cancer clinical trials with pain as a self-reported outcome.