Howard Homesley | Wake Forest University School of Medicine (original) (raw)
Papers by Howard Homesley
Gynecologic Oncology, 1987
American Journal of Clinical Oncology-cancer Clinical Trials, 1985
Twenty patients with advanced or recurrent uterine sarcoma no longer amenable to control with sur... more Twenty patients with advanced or recurrent uterine sarcoma no longer amenable to control with surgery and/or radiotherapy were entered into study by Gynecologic Oncology Group institutions to receive piperazinedione 9 mg/m2 intravenously every 3 weeks. One patient was deemed to be ineligible for study. Among the 19 evaluable patients, only one response was observed, a partial response in a patient with leiomyosarcoma. Adverse effects consisted primarily of myelosuppression and were tolerable. Piperazinedione at the dose and schedule tested appears to have little activity against uterine sarcomas.
Gynecologic Oncology, 1986
Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control... more Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control with surgery and/or radiotherapy were entered into a phase II study of cisplatin 50 mg/m2 intravenously every 3 weeks. Two were deemed ineligible because of a primary site of origin other than vagina. Two were deemed inevaluable, one because of the lack of measurable disease and the other because she never received drug. The remaining 22 included a variety of histologies (16 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 clear cell carcinoma, 1 leiomyosarcoma, and 2 carcinomas not otherwise specified). One complete responder was observed among the 16 patients with squamous cell carcinoma. Adverse effects were tolerable and were essentially those reported in other series. These results suggest that cisplatin has insignificant activity in advanced or recurrent squamous cell carcinoma of the vagina at least at the dose and schedule tested. No comment can be made regarding the activity of cisplatin in other histologies.
Gynecologic Oncology, 2004
Objectives. Carcinosarcomas of the ovary are rare; hence, although most patients recur after surg... more Objectives. Carcinosarcomas of the ovary are rare; hence, although most patients recur after surgical resection or have metastatic disease at the time of diagnosis, only anecdotal information is available concerning the activity of cytotoxic drugs against these lesions. The Gynecologic Oncology Group (GOG) initiated a concerted effort to study cytotoxic therapy for these cancers in 1976. This report presents data
Gynecologic Oncology, 1985
Pseudomyxoma peritonei is a rare disease characteristically secondary to mucin-producing adenocar... more Pseudomyxoma peritonei is a rare disease characteristically secondary to mucin-producing adenocarcinomas of the ovary and appendix. Though, as a rule, not invasive or metastatic, death occurs secondary to gastrointestinal dysfunction. This is the first case of pseudomyxoma peritonei secondary to an ovarian primary possibly cured by systemic cis-platinum, doxorubicin, and cyclophosphamide.
Gynecologic Oncology, 1999
Objectives.The objectives of this study were to assess efficacy and toxicity of the combination o... more Objectives.The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies.Methods.Patients with incompletely resected Stages II–IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2×
Clinical Pharmacology and Therapeutics, 1988
A design is described that uses need for supplemental (rescue) analgesic as a factor predicting e... more A design is described that uses need for supplemental (rescue) analgesic as a factor predicting effectiveness of a test analgesic. This methodology is especially suited for evaluating long-acting analgesics given repeatedly. Rescue use is measured over dosing intervals as test drug is titrated from a subanalgesic dose to that requiring no or minimal rescue. This design was used to evaluate oral long-acting morphine sulfate (MS Contin) given every 12 hours in a crossover study of cancer pain using oral immediaterelease morphine sulfate given every 4 hours as reference. Less morphine was required for MS Contin given every 12 hours relative to immediaterelease morphine sulfate given every 4 hours (186 ± 22 mg vs. 239 ± 35 mg; p = 0.04). Total daily morphine for both regimens correlated linearly (r = 0.96) with a slope of 1.27 ± 0.11, significantly (p = 0.03) different from equivalence (slope of unity) in favor of MS Contin. This design features assay sensitivity (dose-response) and provides relative potency estimates for analgesics given at specific regimens.
Clinical pharmacology and therapeutics, 1988
A design is described that uses need for supplemental (rescue) analgesic as a factor predicting e... more A design is described that uses need for supplemental (rescue) analgesic as a factor predicting effectiveness of a test analgesic. This methodology is especially suited for evaluating long-acting analgesics given repeatedly. Rescue use is measured over dosing intervals as test drug is titrated from a subanalgesic dose to that requiring no or minimal rescue. This design was used to evaluate oral long-acting morphine sulfate (MS Contin) given every 12 hours in a crossover study of cancer pain using oral immediate-release morphine sulfate given every 4 hours as reference. Less morphine was required for MS Contin given every 12 hours relative to immediate-release morphine sulfate given every 4 hours (186 +/- 22 mg vs. 239 +/- 35 mg; p = 0.04). Total daily morphine for both regimens correlated linearly (r = 0.96) with a slope of 1.27 +/- 0.11, significantly (p = 0.03) different from equivalence (slope of unity) in favor of MS Contin. This design features assay sensitivity (dose-response)...
Forty-nine evaluable patients with advanced or recurrent endometrial carcinoma who were no longer... more Forty-nine evaluable patients with advanced or recurrent endometrial carcinoma who were no longer controllable with surgery, radiotherapy, and hormonal therapy and who had not received prior chemotherapy were treated with cisplatin 50 mg/m* intravenously every 3 weeks. Two complete responses (4%) and eight partial responses (16%) were observed among the 49 patients. Twenty-two (45%) exhibited stable disease for at least 2 months, while 17 patients (35%) progressed less than 2 months after initiating chemotherapy. Adverse effects included mild leukopenia (31%), nausea and vomiting (72%), and mild azotemia (51%). Only 2 patients experienced life-threatening toxicity; one related to renal failure and the other to sepsis and shock. Cisplatin thus has delinite activity when given at the dose and schedule tested to patients with endometrial carcinoma who have not received prior chemotherapy. 0 1989 Academic J?ms, Inc.
International Journal of Gynecology & Obstetrics, 1990
Adoptive ceiluinr immunotherapg to the endometriai carciaoma ceii iine xeoografts in nnde mice Gy... more Adoptive ceiluinr immunotherapg to the endometriai carciaoma ceii iine xeoografts in nnde mice Gynecoiogic Oncology; 34/2 (195-199)/1989/ The present study was designed to examine the immunotherapeutic properties of lymphokine-activated killer (LAK) cells against uterine endometrial cancers. Three endometrial cancer ceii iines, ISHIKAWA, SNG-M, and HHUA, were shown to be specificaliy iysed in short-term "'Cr-release assay, although the susceptibility was different among the ceii iines. The xenograft tumors of ISHIKAWA and SNG-M exhibited high susceptibility to LAK ceiis in the in vitro assay and responded wel1 to the adoptive transfer of LAK cells in nude mice. On the other hand, the xenograft of HHUA showed low reactivity in LAK cells and showed no response to the adoptive immunotherapy. However, the adoptive transfer of LAK celis combined with intraperitoneal administration of both recombinant interieukin-2 (rIL-2) and lentinan markedly inhibited the growth of HHUA xenografts in nude mice, while no response was observed in nude mice treated with LAK cells plus either rIL-2 or lentinan, or treated with rIL-2 plus lentinan alone. These results suggest the clinical application of adoptive immunotherapy in association with LAK cells, rIL-2, and lentinan as a treatment of gynecoiogic cancers.
Gynecologic Oncology, 1986
Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the vulva no longer a... more Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the vulva no longer amenable to control with surgery and/or radiotherapy were entered onto one of two phase II studies. One was deemed ineligible because of a primary site of origin other than vulva. Of the remaining 37, 13 patients received piperazinedione 9 mg/m2 iv every 3 weeks. No objective regressions were observed. Five patients were judged to have had stable disease, while eight demonstrated increasing disease. The other 24 patients received cisplatin 50 mg/m2 iv every 3 weeks. Of the 22 who were evaluable for response because of the presence of measurable disease, no objective regression of disease was observed. Ten had stable disease, while the remaining 12 had increasing disease. Adverse effects were tolerable for each study agent and were essentially those reported in other series for these two drugs. These results suggest that neither agent is active in advanced or recurrent squamous cell carcinoma of the vulva at least at the dose and schedule tested.
Journal of Translational Medicine, 2012
Background: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK... more Background: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. Methods: A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay.
Journal of Clinical Oncology, 2007
To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carci... more To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma (CS) improves overall survival (OS), progression-free survival (PFS), response, and toxicity. Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m2 intravenously (IV) daily for 3 days (arm 1) or ifosfamide 1.6 g/m2 IV daily for 3 days plus paclitaxel 135 mg/m2 by 3-hour infusion day 1 (arm 2). Mesna was administered similarly (both arms); filgrastim began on day 4 (arm 2). Cycles were repeated every 21 days up to eight cycles. Of 214 patients enrolled, 179 were eligible (arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy (grade 1 to 4; 8% v 30%). The crude response rate was 29% (arm 1) and 45% (arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 (P = .017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P = .03) and a 29% decrease in the hazard of progression (HR, 0.71; 95% CI, 0.51 to 0.97; P = .03) relative to arm 1 when stratifying by performance status. OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.
International Journal of Radiation Oncology*Biology*Physics, 1996
Purpose: To determine outcomes and treatment toxicities in patients with optimal (11 cm residual)... more Purpose: To determine outcomes and treatment toxicities in patients with optimal (11 cm residual) Stage man carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAD Methods and Materials: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIL4 (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papibary (n = 21,50%); other (n = 21,50%); Grade 1 (n = 1,2%); 2 (n = 14,33%); 3 (n = 27,54%); residual disease after initial surgery (present: n = 23, 55%; absent: II = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients.
International Journal of Gynecology & Obstetrics, 1991
pituitary gland. We describe a patient with secondary amenorrhea and galactorrhea in whom such an... more pituitary gland. We describe a patient with secondary amenorrhea and galactorrhea in whom such an elevated prolactin level did initially lead to the discovery of a pituitary mass that was treated first unsuccessfully with surgery, and then successfully with medical therapy. After medical therapy normal menstruation continued, galactorrhea recurred intermittently, and the prolactin level rose again and remained in the m 36 pg/L range. However, 2 years later an ovarian teratoma was discovered incidentally and was removed surgically. On pathological evaluation the teratoma was noted to include prolactin-containing tissue, and immediately after surgery the patient's prolactin level and responsiveness to stimulatory testing returned to normal. To our knowledge this is the first case report of the association of clinically evident hyperprolactinemia with an ovarian cystic teratoma that contained prolactin-producing tissue. GYNECOL ONCOL 1999,37/l (21-23) Seventeen patients with recurrent cervical cancer were prospectively treated with a combination of bleomycin, vincristine, and mitomycin C (EOM). All patients had previously failed a cis-platinum-containing combination regimen. There were no complete responses. Four patients had partial responses, six patients had stable disease, and seven patients had no response. The median length of survival for responders was the same as that for nonresponders (5 months). More than 50% of patients experienced significant toxicity. The combination of bleomycin, vincristine, and mitomycin C appears to be ineffective as a second-line chemotherapy regimen against recurrent cervical cancer previously treated with cis-platinum.
International Journal of Cancer, 1985
A human tumor clonogenic assay has been used to test the antiproliferative effect of recombinant ... more A human tumor clonogenic assay has been used to test the antiproliferative effect of recombinant human leukocyte interferon alpha2 alone and in combination with each of 8 cytotoxic agents. Cell lines derived from 6 human tumors and primary tumor cells from 13 patients have been used in these clonogenic assay 4T0 whom requests for reprints should be addressed, at the
Gynecologic Oncology, 1989
Factors investigated included recurrences and survival in addition to the early and delayed morbi... more Factors investigated included recurrences and survival in addition to the early and delayed morbidity associated with this operative approach. Recurrent intraepithelial or minimally invasive cancer was documented in six patients, five of whom were treated successfully by a subsequent wide local excision following initial surgery. Only one patient died of recurrent carcinoma 16 months following surgery. The morbidity with this operation was appreciably less than that generally reported with more extensive operations commonly employed in the management of vulvar cancer and is recommended for management of patients with early invasive disease. GYNECOL ONCOL 1989,35/3 (378-382) One hundred eighty-six patients with minimal residual Stage III ovarian cancer (tumor mass C 3 cm) were treated in a prospective randomized protocol (melphalan with or without Corynebacterium parvum). As per protocol 84 patients were eligible and underwent a second-look laparotomy with 41 (49%) having negative findings for persistent malignancy. Factors which affected survival after second look were presence or absence of macroscopic disease, age, and grade. Depending upon these prognostic factors, survival at 4 years after second look ranged from 31 to 100%. The role of second-look laparotomy is examined relative to these results.
Gynecologic Oncology, 1996
AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for int... more AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for intraperitoneal (ip) administration in a phase 2 trial involving 25 patients with advanced gynecologic malignancies. At an AD-32 dose of 600 mg/m2, the limiting toxicity was grade 4 neutropenia (64% of patients), while severe abdominal pain was relatively uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compared to the systemic compartment. At the 600 mg/m2 dose level, 4 of 9 patients (44%) with ascites experienced control of malignant fluid reaccumulation. Based on the results of this phase 1 trial, further exploration of a possible role for the ip administration of AD-32 in individuals with gynecological malignancies appears indicated, particularly in patients with either small volume residual disease after initial systemic chemotherapy or in those with intractable ascites.
Gynecologic Oncology, 1992
The Gynecologic Oncology Group conducted a phase II trial of intraperitoneal (ip) cisplatin plus ... more The Gynecologic Oncology Group conducted a phase II trial of intraperitoneal (ip) cisplatin plus recombinant human alpha-interferon in patients with small-volume persistent/recurrent ovarian cancer. This study was based on the known single agent activity of the drugs administered by the ip route and experimental evidence of cytotoxic synergy between the agents. In 18 evaluable patients, only 1 partial response was observed (5.5% response rate). In an effort to explain these disappointing findings, patients were retrospectively divided into two groups; those with favorable disease (documented response to systemic platinum and absence of surgical findings of diffuse carcinomatosis at laparotomy prior to initiation of ip therapy) or unfavorable disease (no evidence of response to systemic platinum and/or laparotomy findings of diffuse carcinomatosis before ip treatment). The favorable patient population would be predicted to have a far greater chance of responding to local therapy, but only 3 of the evaluable patients fell into this category. In the 15 unfavorable patients, only 1 partial response was observed (7% response rate). We conclude that patients who have failed to demonstrate a response to systemic cisplatin or carboplatin or who have diffuse carcinomatosis at second-look laparotomy are poor candidates for second-line ip cisplatin-based therapy, even if they are considered to have small-volume residual disease (each individual tumor nodules less than 0.5-1 cm). Such patients should be considered for alternative therapeutic strategies.
Gynecologic Oncology, 1990
The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiatio... more The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiation therapy for endometrial carcinoma in a randomized, prospective manner. The study population consisted of patients clinically stage I or II (occult) who, after surgical-pathologic evaluation, had one or more risk factors for recurrence: greater than 50% myometrial invasion, pelvic or aortic node metastasis, cervical involvement, or adnexal metastases. All patients without aortic node metastasis received 5000 rads to the whole pelvis at 160-180 rads per day. If aortic node metastasis was documented, aortic field radiation to the top of T12 was offered. The aortic target dose was 4500 rads at 150 rads per day. After completion of radiation therapy, the patients were randomized to receive doxorubicin bolus therapy (60 mg/m' starting dose) to a maximum cumulative dose of 500 mg/m'. Between November 1977 and July 1986, 92 patients were entered into the doxorubicin (DGX) treatment arm, and 89 patients entered the noDOX arm. There was no statistically significant difference in survival or progression-free interval of the two arms. The 5-year survival rates for patients with deep myometrial invasion, cervical involvement, and pelvic node metastases were similar (63-70%), whereas the rate for patients with aortic node metastases was 26%. There was no significant difference in the recurrence pattern between the two treatment arms. There were no cases of grade 3 or 4 cardiac toxicity. Twelve patients (6.9%) developed small bowel obstruction after radiation therapy. There were three treatment-related deaths in the DOX arm and two in the radiation therapy-only arm. We conclude that, because of protocol violations, small sample size, and the number of patients lost to follow-up, this study was unable to determine what effect use of doxorubicin as adjuvant therapy had on recurrence, pro-*Reprint requests should be sent to COG Administrative Office,
Gynecologic Oncology, 1987
American Journal of Clinical Oncology-cancer Clinical Trials, 1985
Twenty patients with advanced or recurrent uterine sarcoma no longer amenable to control with sur... more Twenty patients with advanced or recurrent uterine sarcoma no longer amenable to control with surgery and/or radiotherapy were entered into study by Gynecologic Oncology Group institutions to receive piperazinedione 9 mg/m2 intravenously every 3 weeks. One patient was deemed to be ineligible for study. Among the 19 evaluable patients, only one response was observed, a partial response in a patient with leiomyosarcoma. Adverse effects consisted primarily of myelosuppression and were tolerable. Piperazinedione at the dose and schedule tested appears to have little activity against uterine sarcomas.
Gynecologic Oncology, 1986
Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control... more Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control with surgery and/or radiotherapy were entered into a phase II study of cisplatin 50 mg/m2 intravenously every 3 weeks. Two were deemed ineligible because of a primary site of origin other than vagina. Two were deemed inevaluable, one because of the lack of measurable disease and the other because she never received drug. The remaining 22 included a variety of histologies (16 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 clear cell carcinoma, 1 leiomyosarcoma, and 2 carcinomas not otherwise specified). One complete responder was observed among the 16 patients with squamous cell carcinoma. Adverse effects were tolerable and were essentially those reported in other series. These results suggest that cisplatin has insignificant activity in advanced or recurrent squamous cell carcinoma of the vagina at least at the dose and schedule tested. No comment can be made regarding the activity of cisplatin in other histologies.
Gynecologic Oncology, 2004
Objectives. Carcinosarcomas of the ovary are rare; hence, although most patients recur after surg... more Objectives. Carcinosarcomas of the ovary are rare; hence, although most patients recur after surgical resection or have metastatic disease at the time of diagnosis, only anecdotal information is available concerning the activity of cytotoxic drugs against these lesions. The Gynecologic Oncology Group (GOG) initiated a concerted effort to study cytotoxic therapy for these cancers in 1976. This report presents data
Gynecologic Oncology, 1985
Pseudomyxoma peritonei is a rare disease characteristically secondary to mucin-producing adenocar... more Pseudomyxoma peritonei is a rare disease characteristically secondary to mucin-producing adenocarcinomas of the ovary and appendix. Though, as a rule, not invasive or metastatic, death occurs secondary to gastrointestinal dysfunction. This is the first case of pseudomyxoma peritonei secondary to an ovarian primary possibly cured by systemic cis-platinum, doxorubicin, and cyclophosphamide.
Gynecologic Oncology, 1999
Objectives.The objectives of this study were to assess efficacy and toxicity of the combination o... more Objectives.The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies.Methods.Patients with incompletely resected Stages II–IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2×
Clinical Pharmacology and Therapeutics, 1988
A design is described that uses need for supplemental (rescue) analgesic as a factor predicting e... more A design is described that uses need for supplemental (rescue) analgesic as a factor predicting effectiveness of a test analgesic. This methodology is especially suited for evaluating long-acting analgesics given repeatedly. Rescue use is measured over dosing intervals as test drug is titrated from a subanalgesic dose to that requiring no or minimal rescue. This design was used to evaluate oral long-acting morphine sulfate (MS Contin) given every 12 hours in a crossover study of cancer pain using oral immediaterelease morphine sulfate given every 4 hours as reference. Less morphine was required for MS Contin given every 12 hours relative to immediaterelease morphine sulfate given every 4 hours (186 ± 22 mg vs. 239 ± 35 mg; p = 0.04). Total daily morphine for both regimens correlated linearly (r = 0.96) with a slope of 1.27 ± 0.11, significantly (p = 0.03) different from equivalence (slope of unity) in favor of MS Contin. This design features assay sensitivity (dose-response) and provides relative potency estimates for analgesics given at specific regimens.
Clinical pharmacology and therapeutics, 1988
A design is described that uses need for supplemental (rescue) analgesic as a factor predicting e... more A design is described that uses need for supplemental (rescue) analgesic as a factor predicting effectiveness of a test analgesic. This methodology is especially suited for evaluating long-acting analgesics given repeatedly. Rescue use is measured over dosing intervals as test drug is titrated from a subanalgesic dose to that requiring no or minimal rescue. This design was used to evaluate oral long-acting morphine sulfate (MS Contin) given every 12 hours in a crossover study of cancer pain using oral immediate-release morphine sulfate given every 4 hours as reference. Less morphine was required for MS Contin given every 12 hours relative to immediate-release morphine sulfate given every 4 hours (186 +/- 22 mg vs. 239 +/- 35 mg; p = 0.04). Total daily morphine for both regimens correlated linearly (r = 0.96) with a slope of 1.27 +/- 0.11, significantly (p = 0.03) different from equivalence (slope of unity) in favor of MS Contin. This design features assay sensitivity (dose-response)...
Forty-nine evaluable patients with advanced or recurrent endometrial carcinoma who were no longer... more Forty-nine evaluable patients with advanced or recurrent endometrial carcinoma who were no longer controllable with surgery, radiotherapy, and hormonal therapy and who had not received prior chemotherapy were treated with cisplatin 50 mg/m* intravenously every 3 weeks. Two complete responses (4%) and eight partial responses (16%) were observed among the 49 patients. Twenty-two (45%) exhibited stable disease for at least 2 months, while 17 patients (35%) progressed less than 2 months after initiating chemotherapy. Adverse effects included mild leukopenia (31%), nausea and vomiting (72%), and mild azotemia (51%). Only 2 patients experienced life-threatening toxicity; one related to renal failure and the other to sepsis and shock. Cisplatin thus has delinite activity when given at the dose and schedule tested to patients with endometrial carcinoma who have not received prior chemotherapy. 0 1989 Academic J?ms, Inc.
International Journal of Gynecology & Obstetrics, 1990
Adoptive ceiluinr immunotherapg to the endometriai carciaoma ceii iine xeoografts in nnde mice Gy... more Adoptive ceiluinr immunotherapg to the endometriai carciaoma ceii iine xeoografts in nnde mice Gynecoiogic Oncology; 34/2 (195-199)/1989/ The present study was designed to examine the immunotherapeutic properties of lymphokine-activated killer (LAK) cells against uterine endometrial cancers. Three endometrial cancer ceii iines, ISHIKAWA, SNG-M, and HHUA, were shown to be specificaliy iysed in short-term "'Cr-release assay, although the susceptibility was different among the ceii iines. The xenograft tumors of ISHIKAWA and SNG-M exhibited high susceptibility to LAK ceiis in the in vitro assay and responded wel1 to the adoptive transfer of LAK cells in nude mice. On the other hand, the xenograft of HHUA showed low reactivity in LAK cells and showed no response to the adoptive immunotherapy. However, the adoptive transfer of LAK celis combined with intraperitoneal administration of both recombinant interieukin-2 (rIL-2) and lentinan markedly inhibited the growth of HHUA xenografts in nude mice, while no response was observed in nude mice treated with LAK cells plus either rIL-2 or lentinan, or treated with rIL-2 plus lentinan alone. These results suggest the clinical application of adoptive immunotherapy in association with LAK cells, rIL-2, and lentinan as a treatment of gynecoiogic cancers.
Gynecologic Oncology, 1986
Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the vulva no longer a... more Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the vulva no longer amenable to control with surgery and/or radiotherapy were entered onto one of two phase II studies. One was deemed ineligible because of a primary site of origin other than vulva. Of the remaining 37, 13 patients received piperazinedione 9 mg/m2 iv every 3 weeks. No objective regressions were observed. Five patients were judged to have had stable disease, while eight demonstrated increasing disease. The other 24 patients received cisplatin 50 mg/m2 iv every 3 weeks. Of the 22 who were evaluable for response because of the presence of measurable disease, no objective regression of disease was observed. Ten had stable disease, while the remaining 12 had increasing disease. Adverse effects were tolerable for each study agent and were essentially those reported in other series for these two drugs. These results suggest that neither agent is active in advanced or recurrent squamous cell carcinoma of the vulva at least at the dose and schedule tested.
Journal of Translational Medicine, 2012
Background: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK... more Background: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. Methods: A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay.
Journal of Clinical Oncology, 2007
To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carci... more To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma (CS) improves overall survival (OS), progression-free survival (PFS), response, and toxicity. Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m2 intravenously (IV) daily for 3 days (arm 1) or ifosfamide 1.6 g/m2 IV daily for 3 days plus paclitaxel 135 mg/m2 by 3-hour infusion day 1 (arm 2). Mesna was administered similarly (both arms); filgrastim began on day 4 (arm 2). Cycles were repeated every 21 days up to eight cycles. Of 214 patients enrolled, 179 were eligible (arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy (grade 1 to 4; 8% v 30%). The crude response rate was 29% (arm 1) and 45% (arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 (P = .017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P = .03) and a 29% decrease in the hazard of progression (HR, 0.71; 95% CI, 0.51 to 0.97; P = .03) relative to arm 1 when stratifying by performance status. OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.
International Journal of Radiation Oncology*Biology*Physics, 1996
Purpose: To determine outcomes and treatment toxicities in patients with optimal (11 cm residual)... more Purpose: To determine outcomes and treatment toxicities in patients with optimal (11 cm residual) Stage man carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAD Methods and Materials: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIL4 (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papibary (n = 21,50%); other (n = 21,50%); Grade 1 (n = 1,2%); 2 (n = 14,33%); 3 (n = 27,54%); residual disease after initial surgery (present: n = 23, 55%; absent: II = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients.
International Journal of Gynecology & Obstetrics, 1991
pituitary gland. We describe a patient with secondary amenorrhea and galactorrhea in whom such an... more pituitary gland. We describe a patient with secondary amenorrhea and galactorrhea in whom such an elevated prolactin level did initially lead to the discovery of a pituitary mass that was treated first unsuccessfully with surgery, and then successfully with medical therapy. After medical therapy normal menstruation continued, galactorrhea recurred intermittently, and the prolactin level rose again and remained in the m 36 pg/L range. However, 2 years later an ovarian teratoma was discovered incidentally and was removed surgically. On pathological evaluation the teratoma was noted to include prolactin-containing tissue, and immediately after surgery the patient's prolactin level and responsiveness to stimulatory testing returned to normal. To our knowledge this is the first case report of the association of clinically evident hyperprolactinemia with an ovarian cystic teratoma that contained prolactin-producing tissue. GYNECOL ONCOL 1999,37/l (21-23) Seventeen patients with recurrent cervical cancer were prospectively treated with a combination of bleomycin, vincristine, and mitomycin C (EOM). All patients had previously failed a cis-platinum-containing combination regimen. There were no complete responses. Four patients had partial responses, six patients had stable disease, and seven patients had no response. The median length of survival for responders was the same as that for nonresponders (5 months). More than 50% of patients experienced significant toxicity. The combination of bleomycin, vincristine, and mitomycin C appears to be ineffective as a second-line chemotherapy regimen against recurrent cervical cancer previously treated with cis-platinum.
International Journal of Cancer, 1985
A human tumor clonogenic assay has been used to test the antiproliferative effect of recombinant ... more A human tumor clonogenic assay has been used to test the antiproliferative effect of recombinant human leukocyte interferon alpha2 alone and in combination with each of 8 cytotoxic agents. Cell lines derived from 6 human tumors and primary tumor cells from 13 patients have been used in these clonogenic assay 4T0 whom requests for reprints should be addressed, at the
Gynecologic Oncology, 1989
Factors investigated included recurrences and survival in addition to the early and delayed morbi... more Factors investigated included recurrences and survival in addition to the early and delayed morbidity associated with this operative approach. Recurrent intraepithelial or minimally invasive cancer was documented in six patients, five of whom were treated successfully by a subsequent wide local excision following initial surgery. Only one patient died of recurrent carcinoma 16 months following surgery. The morbidity with this operation was appreciably less than that generally reported with more extensive operations commonly employed in the management of vulvar cancer and is recommended for management of patients with early invasive disease. GYNECOL ONCOL 1989,35/3 (378-382) One hundred eighty-six patients with minimal residual Stage III ovarian cancer (tumor mass C 3 cm) were treated in a prospective randomized protocol (melphalan with or without Corynebacterium parvum). As per protocol 84 patients were eligible and underwent a second-look laparotomy with 41 (49%) having negative findings for persistent malignancy. Factors which affected survival after second look were presence or absence of macroscopic disease, age, and grade. Depending upon these prognostic factors, survival at 4 years after second look ranged from 31 to 100%. The role of second-look laparotomy is examined relative to these results.
Gynecologic Oncology, 1996
AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for int... more AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for intraperitoneal (ip) administration in a phase 2 trial involving 25 patients with advanced gynecologic malignancies. At an AD-32 dose of 600 mg/m2, the limiting toxicity was grade 4 neutropenia (64% of patients), while severe abdominal pain was relatively uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compared to the systemic compartment. At the 600 mg/m2 dose level, 4 of 9 patients (44%) with ascites experienced control of malignant fluid reaccumulation. Based on the results of this phase 1 trial, further exploration of a possible role for the ip administration of AD-32 in individuals with gynecological malignancies appears indicated, particularly in patients with either small volume residual disease after initial systemic chemotherapy or in those with intractable ascites.
Gynecologic Oncology, 1992
The Gynecologic Oncology Group conducted a phase II trial of intraperitoneal (ip) cisplatin plus ... more The Gynecologic Oncology Group conducted a phase II trial of intraperitoneal (ip) cisplatin plus recombinant human alpha-interferon in patients with small-volume persistent/recurrent ovarian cancer. This study was based on the known single agent activity of the drugs administered by the ip route and experimental evidence of cytotoxic synergy between the agents. In 18 evaluable patients, only 1 partial response was observed (5.5% response rate). In an effort to explain these disappointing findings, patients were retrospectively divided into two groups; those with favorable disease (documented response to systemic platinum and absence of surgical findings of diffuse carcinomatosis at laparotomy prior to initiation of ip therapy) or unfavorable disease (no evidence of response to systemic platinum and/or laparotomy findings of diffuse carcinomatosis before ip treatment). The favorable patient population would be predicted to have a far greater chance of responding to local therapy, but only 3 of the evaluable patients fell into this category. In the 15 unfavorable patients, only 1 partial response was observed (7% response rate). We conclude that patients who have failed to demonstrate a response to systemic cisplatin or carboplatin or who have diffuse carcinomatosis at second-look laparotomy are poor candidates for second-line ip cisplatin-based therapy, even if they are considered to have small-volume residual disease (each individual tumor nodules less than 0.5-1 cm). Such patients should be considered for alternative therapeutic strategies.
Gynecologic Oncology, 1990
The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiatio... more The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiation therapy for endometrial carcinoma in a randomized, prospective manner. The study population consisted of patients clinically stage I or II (occult) who, after surgical-pathologic evaluation, had one or more risk factors for recurrence: greater than 50% myometrial invasion, pelvic or aortic node metastasis, cervical involvement, or adnexal metastases. All patients without aortic node metastasis received 5000 rads to the whole pelvis at 160-180 rads per day. If aortic node metastasis was documented, aortic field radiation to the top of T12 was offered. The aortic target dose was 4500 rads at 150 rads per day. After completion of radiation therapy, the patients were randomized to receive doxorubicin bolus therapy (60 mg/m' starting dose) to a maximum cumulative dose of 500 mg/m'. Between November 1977 and July 1986, 92 patients were entered into the doxorubicin (DGX) treatment arm, and 89 patients entered the noDOX arm. There was no statistically significant difference in survival or progression-free interval of the two arms. The 5-year survival rates for patients with deep myometrial invasion, cervical involvement, and pelvic node metastases were similar (63-70%), whereas the rate for patients with aortic node metastases was 26%. There was no significant difference in the recurrence pattern between the two treatment arms. There were no cases of grade 3 or 4 cardiac toxicity. Twelve patients (6.9%) developed small bowel obstruction after radiation therapy. There were three treatment-related deaths in the DOX arm and two in the radiation therapy-only arm. We conclude that, because of protocol violations, small sample size, and the number of patients lost to follow-up, this study was unable to determine what effect use of doxorubicin as adjuvant therapy had on recurrence, pro-*Reprint requests should be sent to COG Administrative Office,