Echinomycin (NSC 526417) in squamous-cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group

Twenty-eight evaluable patients with advanced or recurrent squamous-cell carcinoma of the cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. All patients had prior chemotherapy. Two patients had partial responses (7% response, 95% confidence interval for response of 1 to 24%). The major toxicity was nausea and vomiting. Myelosuppression and other toxicity were modest. Echinomycin, at this dose and schedule, displays minimal activity in patients with squamous-cell carcinoma of the cervix who have had prior chemotherapy.     

Echinomycin (NSC 526417) in advanced ovarian cancer. A phase II trial of the Gynecologic Oncology Group

Twenty-two patients with recurrent carcinoma of the ovary progressive after initial chemotherapy (21 with cisplatin-based treatment) were entered on a phase II trial utilizing Echinomycin at a dosage of 1,500 micrograms/m2 every 4 weeks. There were two complete responders and no partial responders (9% response, 95% confidence intervals for complete and partial responses of 1-29%). Major toxicity was modest and consisted mainly of nausea and vomiting. Echinomycin displays minimal activity as salvage therapy in women with advanced ovarian cancer at this dose and schedule.     

Aminothiadiazole (NSC 4728) in patients with advanced nonsquamous carcinoma of the cervix. A phase II study of the Gynecologic Oncology Group

Twenty-six evaluable patients with advanced nonsquamous cell cervical cancer were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Sixteen had received prior chemotherapy. Two patients had complete responses neither had received prior chemotherapy; nine had stable disease; 15 had increasing disease. There was a single life-threatening toxic episode. Aminothiadiazole used in this dosage and schedule has minimal activity in previously treated patients with nonsquamous cell carcinoma.     

ICRF-159 (razoxane) in patients with advanced nonsquamous cell carcinoma of the cervix. A Gynecologic Oncology Group study

Twenty-seven patients with measurable, advanced nonsquamous cell carcinoma of the cervix were entered into this Phase II study evaluating the efficacy of ICRF-159 (razoxane). Eighteen of the 27 had adenocarcinoma. Thirteen patients had no previous chemotherapy. One patient was ineligible because she was never treated. One patient was inevaluable for response. Thus, 25 evaluable patients were given ICRF-159 orally at a starting dose of 1.5 g/m2 weekly until response could be determined. Grade 4 hematologic toxicity in two patients was the only life-threatening toxicity. One study patient had a partial response, 13 patients were regarded as having stable disease, and 11 had increasing disease. We conclude that ICRF-159 administered at this dose and schedule has no significant clinical activity against advanced adenocarcinoma of the cervix.     

A phase II trial of pyrazoloacridine (PZA) in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study

PURPOSE: The Gynecologic Oncology Group performed a phase II study to determine the response rate to pyrazoloacridine (PZA) in patients with advanced, persistent or recurrent squamous carcinoma of the cervix. METHODS: PZA was administered intravenously over 3 h every 3 weeks. A dose of 760 mg/m(2) was given to the first 11 patients and was reduced to 560 mg/m(2) for subsequent patients. The dose reduction was undertaken because of unexpected severe neutropenia among the initial patients. RESULTS: Among 24 evaluable patients, 21 of whom had prior chemotherapy, there was one, brief, complete response (4.2%) and no partial responses. The major toxicity was neutropenia. CONCLUSION: PZA at the dose and schedule employed, has insignificant activity in this population.     

A phase II trial of gallium nitrate (NSC #15200) in previously treated ovarian carcinoma. A Gynecologic Oncology Group Study

Twenty-six evaluable patients with advanced or recurrent epithelial ovarian cancer were treated with 750 mg/m2 of gallium nitrate every three weeks. All patients had prior cisplatin chemotherapy. One patient had a complete response (3.8%), two patients had partial responses (7.7%), and six patients had stable disease (23.1%). The 95% upper confidence bound for response is 27.2%. The major toxicity was nausea and vomiting which was modest, and anemia, which was moderate to severe. Myelosuppression was minimal. Gallium nitrate has modest activity in previously treated patients with epithelial ovarian cancer.     

5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group.

Twenty-eight patients with recurrent squamous carcinoma of the cervix not amenable to cure by further surgery or radiation therapy were entered into a Phase II trial utilizing i.v. leucovorin 20 mg/m2 followed by 5-fluorouracil 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. One patient never received therapy, and three are inevaluable for response; therefore, 27 patients were evaluable for toxicity and 24 for response. Twenty-three patients had received prior radiotherapy, and 16 had received prior chemotherapy. There was one partial response 4.2% (95% confidence intervals for a response of 0 to 21%). Although toxicity was acceptable with 11 of 27 (41%) grade 3 or 4 leukopenia, 1 of 27 (4%) grade 3 thrombocytopenia, and 3 of 27 (11%) grade 3 or 4 gastrointestinal toxicity, this dose schedule of 5-fluorouracil and leucovorin has minimal activity in recurrent squamous carcinoma of the cervix.     

Teniposide (VM-26) in patients with non-squamous-cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group

Twenty-three evaluable patients with non-squamous-cell carcinoma of the cervix were treated with teniposide 100 mg/m2 per week administered as a 30-60 min infusion. Escalations of 20 mg/m2 per week to a maximum dose of 160 mg/m2 were performed in patients without toxicity. Thirteen of the 23 patients had no prior chemotherapy. One patient had a partial response (95% confidence intervals for response less than or equal to 19%). Toxicity was minimal. Seven patients had white blood cell counts of less than 2,000/mm3 but only one had less than 1,000/mm3. No patients had platelet counts less than 50,000/mm3, and no bleeding or septic episodes were noted. Two patients had mild nausea and seven had mild nausea and vomiting. Teniposide displays no major activity in patients with non-squamous-cell cervical cancer.     

Aminothiadiazole (NSC 4728) in patients with advanced ovarian carcinoma. A phase II study of the Gynecologic Oncology Group

Thirty-two evaluable patients with advanced epithelial ovarian cancer were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Two patients had partial responses, 12 had stable disease, 16 had increasing disease, and two were inevaluable for response. Aminothiadiazole used in this dosage and schedule has minimal activity in ovarian carcinoma patients previously treated.     

Phase II trial of piperazinedione (NSC 135758) in the treatment of advanced or recurrent carcinoma of the ovary. A Gynecologic Oncology Group study

Thirty-eight patients with advanced or recurrent epithelial ovarian cancer no longer amenable to management with surgery, radiotherapy, or chemotherapy with known activity were given piperazinedione 9 mg/m2 intravenously every 3 weeks. Of the 31 patients evaluable for response, only one achieved a partial response of disease (3%), while there were no complete responses. Fourteen (45%) experienced progression of disease less than 1 month after starting therapy. Adverse effects consisted primarily of myelosuppression (81%), nausea and vomiting (32%), and azotemia (29%) with three patients (10%) having life-threatening thrombocytopenia. While adverse effects were tolerated, the drug at the dose and schedule tested has only minimal activity at best and should not be considered for further trials in epithelial ovarian cancer.     

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.     

A phase II study of PALA (NSC 224131) in patients with advanced ovarian carcinoma. A Gynecologic Oncology Group study

Pala, 5G /M2 i.v. every 3 weeks was given to 32 evaluable patients with ovarian carcinoma (31 previously treated). No complete or partial responses were noted. Ten patients had stable disease for a median progression-free interval of 4.7+ months, while the remainder had progression of disease from the start of therapy. The major toxicity was dermatologic, and five patients had severe skin rash with desquamation or ulceration. There was no substantial hematologic or gastrointestinal toxicity. PALA displays no useful activity in previously-treated patients with ovarian cancer.     

Phase II trial of piperazinedione (NCS 135758) in the treatment of advanced or recurrent squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study

Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to management with surgery and/or radiotherapy were given piperazinedione 9 mg/m2 intravenously every 3 weeks. Five (13%) experienced either complete or partial regression of disease, while 13 (34%) demonstrated stable disease. Responses were relatively short (median 3 months) with responders surviving significantly longer than nonresponders (median 20.3 months vs. 3.0 months, p = 0.01). Adverse effects consisted primarily of myelosuppression (61%) and nausea and vomiting (47%) and generally were mild to moderate and tolerable. The drug has minimal activity and tolerable adverse effects and could be considered for trials of combination chemotherapy in this disease.     

PALA (NSC-224131) in advanced carcinoma of the cervix. A phase II study of the Gynecologic Oncology Group

Thirty-six patients with advanced carcinoma of the cervix received PALA at a dosage of 5 gm/m2 every three weeks. Thirty-three patients had received prior irradiation therapy and chemotherapy. No complete or partial responses were seen. The major toxicity was dermatologic and occurred in 16/36 (44%) of patients. Three patients experienced dose limiting disorientation or confusion. PALA was not associated with any antitumor activity in patients with advanced carcinoma of the cervix who had received prior chemotherapy. The results of this study indicate that PALA has no substantial activity in patients with advanced squamous carcinoma of the cervix who have previously received chemotherapy.     

Aminothiadiazole (NSC #4728) in patients with advanced cervical carcinoma. A phase II study of the Gynecologic Oncology Group

Twenty-one evaluable patients with advanced squamous-cell cervical cancer were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Nineteen had prior chemotherapy. One patient had a partial response; six had stable disease; 14 had increasing disease; and two were unevaluable for response. There was a single life-threatening toxic episode. Aminothiadiazole used in this dosage and schedule has minimal activity in previously treated cervical carcinoma patients.     

Phase I trial of cisplatin and razoxane (ICRF-159) (NSC #119875) in advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Pilot Study

Both cisplatin and razoxane have shown activity in squamous carcinoma of the cervix. Cisplatin at a dose of 50 mg/m2 intravenously every 21 days was combined with razoxane at two dose levels--750 mg/m2 weekly and 1150 mg/m2 weekly. Three patients were treated at the first dose level and six patients were treated at the second dose level of razoxane. No objective regressions were observed, and three patients refused to continue therapy at the higher dose of razoxane because of nausea and vomiting. Further study of this regimen in cervical cancer is not recommended.     

A phase II clinical trial of diaziquone in the treatment of patients with recurrent endometrial carcinoma. A Gynecologic Oncology Group study

Twenty-six patients with measurable endometrial cancer refractory to standard therapy received AZQ [1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)3,6,dioxo,diethyl ester, NSC 182986] 22.5 mg/m2 diluted in 150 ml normal saline intravenously every three weeks. Thirteen patients experienced no toxicity and the dose in those patients was increased to 30 mg/m2 after the first course. The median number of courses given was 2.5 (range 1-9). The leukocyte count fell below 3000/microliter in 12 patients, and below 1000/microliter in two. The platelet count fell below 100,000/microliter in 12 patients, and below 25,000/microliter in one. Cumulative hematologic toxicity was not seen. One clinical complete response and one partial response were observed. Eight patients had stable disease. Median time to disease progression was 2 months. Median survival was 5.9 months. At this dose and schedule AZQ does not appear to have significant activity in recurrent endometrial cancer.     

Teniposide (VM-26) in patients with advanced endometrial carcinoma. A phase II trial of the Gynecologic Oncology Group

Twenty-two evaluable patients with advanced endometrial cancer were treated with teniposide 100 mg/m2/week administered as a 30-60-minute infusion. Escalations of 20 mg/m2/week to a maximum dose of 160 mg/m2 were performed in patients without toxicity. Seventeen of the 22 patients had prior chemotherapy. Two patients had a partial response (95% upper confidence bound for response: 25.9%). Toxicity was minimal. Four patients had white blood cell counts of less than 2,000/mm3 but only two with less than 1,000/mm3. Only one patient had a platelet count between 25,000 and 50,000, and no bleeding or septic episodes were noted. Four patients had mild nausea, and eight mild nausea and vomiting. Teniposide displays no major activity in patients with advanced endometrial cancer who have had prior chemotherapy.     

5-fluorouracil and low-dose leucovorin in the treatment of recurrent epithelial ovarian carcinoma. A phase II trial of the Gynecologic Oncology Group.

Twenty-one patients with recurrent epithelial ovarian carcinoma not amenable to cure with further surgery or radiotherapy were entered into a Phase II trial utilizing i.v. leucovorin at 20 mg/m2 followed by i.v. 5-fluorouracil at 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. Twenty-one patients were entered. Of these, 20 were eligible for toxicity assessment and 19 for response. Five had received prior radiotherapy, and all had received prior cisplatin-based chemotherapy. There was one patient response (5.3%; 95% confidence intervals for response of 0% to 26%). Toxicity was moderate with 5 of 20 (25%) grade 3 or 4 leukopenia, 12 of 20 (60%) grade 3 or 4 granulocytopenia, 1 of 20 (5%) grade 3 thrombocytopenia, 5 of 20 (25%) grade 3 GI toxicity, and 2 of 20 (10%) grade 3 neurotoxicity. There was one toxic death in a patient who developed granulocytopenia and pneumonia after her third course of treatment. This dose schedule of 5-fluorouracil and leucovorin has minimal activity in patients with recurrent epithelial ovarian carcinoma who have received prior cisplatin chemotherapy.     

Chemotherapy of cervix cancer with mitolactol (dibromodulcitol, NSC 104800) and cisplatin. A phase I study of the Gynecologic Oncology Group.

In this Phase I study, thirteen women with advanced cervix cancer were treated with mitolactol (dibromodulcitol) plus cisplatin to determine a maximum tolerable dose schedule. Response was not an objective of this study, but four partial responses were seen in nine patients with measurable lesions. In general, the therapy was well tolerated, but of the ten patients treated at the first dose level (cisplatin 50 mg/m2 intravenously on day 1 plus mitolactol 180 mg/m2 orally on days 2-6 every 3-4 weeks), 5 required de-escalations and 8 required delays because of toxicity. All three patients treated with cisplatin plus a higher dose of mitolactol (270 mg/m2 x 5) required dose reductions and delays for hematologic toxicity. The first dose level appears tolerable by patients with, and promising in treating, advanced cervix cancer.