Kenneth Webster

Paclitaxel, an Active Agent in Nonsquamous Carcinomas of the Uterine Cervix: A Gynecologic Oncology Group Study

PURPOSE A phase II trial of paclitaxel was initiated in advanced nonsquamous carcinoma of the cervix to determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS Eligible patients had at least one measurable lesion. The starting dose of paclitaxel was 170 mg/m(2) (135 mg/m(2) for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalation to 200 mg/m(2) and de-escalation to 110 mg/m(2) were allowed based on adverse effects. RESULTS In this trial, 42 assessable patients were initially entered onto the study, and 13 responses were seen; four patients had a complete response, and nine patients had a partial response. The overall response rate was 31%. The primary and dose-limiting toxicity was neutropenia. CONCLUSION The response rate to paclitaxel exceeds the rates reported using other single agents in nonsquamous carcinoma of the cervix.

Circadian-timed combination doxorubicin-cisplatin chemotherapy for advanced endometrial carcinoma : a phase II study of the Gynecologic Oncology Group

Patients with advanced or recurrent endometrial cancer of any cell type having measurable disease have been entered into this study to determine the effectiveness and toxicity of circadian-timed doxorubicin-cisplatin chemotherapy. This Phase II study involved no randomization with treatment initiated with doxorubicin 60 mg/m2 over 30 minutes at 6:00 a.m., followed by cisplatin 60 mg/m2 over 30 minutes at 6:00 p.m. every 28 days. Treatment was continued for eight cycles or to a maximum tolerable doxorubicin dose of 480 mg/m2 for patients without progression. Thereafter, responders continued on cisplatin alone. A review of 30 evaluable patients showed 6 (20%) complete responses, 12 (40%) partial responses, and 7 (23%) with stable disease. The number of treatment courses ranged from 2 to 14 with a median of 6.5. the median white blood cell nadir for the 27 patients experiencing leukopenia was 1,600/mm3 (range: 300–3,600/mm3). For the 16 patients experiencing thrombocytopenia the median nadir was 48,500/mm3 (range: 8,000–138,000/mm3). There were no treatment-related deaths. Circadian-timed delivery of doxorubicin-cisplatin chemotherapy was reasonably well tolerated and demonstrated notable response rates in patients with advanced or recurrent endometrial carcinoma.

Circadian-timed combination doxorubicin-cisplatin chemotherapy for advanced endometrial carcinoma

Patients with advanced or recurrent endometrial cancer of any cell type having measurable disease have been entered into this study to determine the effectiveness and toxicity of circadian-timed doxorubicin-cisplatin chemotherapy. This Phase II study involved no randomization with treatment initiated with doxorubicin 60 mg/m2 over 30 minutes at 6:00 a.m., followed by cisplatin 60 mg/m2 over 30 minutes at 6:00 p.m. every 28 days. Treatment was continued for eight cycles or to a maximum tolerable doxorubicin dose of 480 mg/m2 for patients without progression. Thereafter, responders continued on cisplatin alone. A review of 30 evaluable patients showed 6 (20%) complete responses, 12 (40%) partial responses, and 7 (23%) with stable disease. The number of treatment courses ranged from 2 to 14 with a median of 6.5. the median white blood cell nadir for the 27 patients experiencing leukopenia was 1,600/mm3 (range: 300–3,600/mm3). For the 16 patients experiencing thrombocytopenia the median nadir was 48,500/mm3 (range: 8,000–138,000/mm3). There were no treatment-related deaths. Circadian-timed delivery of doxorubicin-cisplatin chemotherapy was reasonably well tolerated and demonstrated notable response rates in patients with advanced or recurrent endometrial carcinoma.

Methotrexate in advanced endometrial carcinoma. A Phase II trial of the Gynecologic Oncology Group

Thirty-three patients with advanced or metastatic endometrial carcinoma were entered in a Phase II trial utilizing methotrexate, 40 mg/m2 intravenously on a weekly basis. Almost all patients had prior total abdominal hysterectomy and almost two-thirds prior pelvic irradiation. No patient had prior chemotherapy. There was one complete and one partial response, for a complete and partial response rate of 6% (95% confidence intervals for a response of 1.7 to 19.6%). Toxicity was mild, with major adverse effects being nausea and vomiting and myelosuppression. One death may have been drug related. Methotrexate displays minimal clinical activity in patients with advanced or recurrent endometrial carcinoma who have received no prior chemotherapy.

Malignant mixed mullerian tumors of the ovary : an analysis of two long-term survivors

Long-term survival following the diagnosis of ovarian malignant mixed mullerian tumor (MMMT) is unusual. This report analyzes two such long-term survivors. One patient presented with a FIGO Stage III, homologous MMMT treated initially with a combination of surgery and chemotherapy. Residual disease, present at the time of initial operation, responded to the chemotherapy; however, the tumor recurred 2½ years postoperatively. This recurrence responded to a combination of surgery and chemotherapy, including continuous adjuvant chemotherapy. This patient is alive, on maintenance chemotherapy, and without evidence of disease, approximately 7 years after the recurrence and 9 years after the initial presentation. The other patient presented with a FIGO Stage III heterologous MMMT treated initially with combined surgery and chemotherapy. Residual disease was present at the time of initial operation. Persistent pelvic disease led to exploratory laparotomy, excision of an 8-cm diameter pelvic mass, and postoperative radiation therapy. The tumor recurred in the left supraclavicular lymph nodes 2 years later (3 years after the initial presentation). This recurrence responded to radiation therapy. This patient was last seen 2 years later (5 years after the initial presentation). At that time, she was without evidence of recurrence. She died 7½ years after her initial presentation. These two patients represent examples of the unusual occurrence of patients with advanced-stage ovarian MMMT experiencing long-term survival following surgical and adjuvant therapy.

Echinomycin (NSC 526417) in recurrent and metastatic nonsquamous cell carcinoma of the cervix: A phase II trial of the Gynecologic Oncology Group

Eighteen evaluable patients with recurrent or metastatic nonsquamous carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. Seven patients had received prior chemotherapy. There was one complete response (5.6%), 95% confidence interval for response of 0-27%. The major toxicity was nausea and vomiting, which was moderate to severe in eight patients. Myelosuppression was minimal. Echinomycin in this dose and schedule displays minimal activity in patients with advanced nonsquamous carcinoma of the cervix.