An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix.

UNLABELLED: Thirty-two evaluable patients with squamous cell cancer of the cervix were treated with i.v. paclitaxel 250 mg/m2 over 3 h every 21 days. They received standard premedications and granulocyte colony stimulating factor (G-CSF) support (5 micrograms/kg/day). Median (range) age was 49 (29-81) years and performance status Zubrod was 1 (0-2). One patient had a complete response and seven patients had a partial response (25%, 95% CI 8-38%). The median survival was 7.3 months. Granulocytopenia was brief and non-cumulative. G-CSF was used for a median (range) of 8 (1-15) days per cycle. IN CONCLUSION: paclitaxel is active in patients with squamous cell cancer of the cervix and is well tolerated in this dose schedule with G-CSF support.

A clinical trial to evaluate the effect of vitamin C supplementation on in vitro mutagen sensitivity. The University of Texas M. D. Anderson Clinical Community Oncology Program Network.

Mutagen sensitivity, as measured by an in vitro assay, has been described as a risk factor for the development of several tobacco-related epithelial cancers. In vitro studies have indicated that sensitivity to the clastogenic effects of bleomycin on chromosomes was reduced with the introduction of ascorbic acid in a dose-dependent relationship. We report the results of a randomized clinical trial to determine whether increasing levels of oral ascorbic acid could reduce the levels of mutagen sensitivity. For this study, we recruited 228 healthy smokers from 21 centers around the country through the Clinical Community Oncology Program. Each individual was randomly assigned to one of four daily regimens: placebo, 1 g of ascorbic acid, 2 g of ascorbic acid, or 4 g of ascorbic acid. Treatments were administered for 16 weeks. Assessment of mutagen sensitivity was made at baseline and at weeks 4, 16, and 20 (4 weeks after cessation of treatment). Serum ascorbic acid levels were measured at baseline and at weeks 4 and 16. Demographic and risk factor data were collected at baseline and at each-measurement point. Analyses measured the differences of mutagen sensitivity levels across the four treatment arms, as well as investigating the correlation between serum ascorbic acid level and mutagen sensitivity levels in individuals. We did not find a dose-response relationship between ascorbic acid intake and mutagen sensitivity. Additionally, we did not find an association between serum ascorbic acid levels and mutagen sensitivity.

Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix.

Twenty-six patients with squamous cell cancer of the cervix were treated with i.v. paclitaxel, 250 mg/m2 over 3 h every 21 days. They received steroid, H1 and H2 blocker premedications, and granulocyte-colony-stimulating factor (G-CSF) support (5 microgram/kg/day). No prior chemotherapy, except as a radiation sensitizer, was allowed. The median age was 50 (range, 36-81) years, and performance status Zubrod was 1 (range, 0-2). Eight (33%) patients had prior surgery, and 22 (92%) had prior radiation therapy. Twenty-four patients were evaluable for response; 2 were later found to be ineligible. Five patients had partial responses (21%; 95% confidence interval, 6-40%), and 14 (58%; 95% confidence interval, 35-78%) had stable disease. The median duration of response was 10 (range, 3-27+) weeks. The responses were within the radiation port (four responses) and outside of it (one response). The median interval from the start of irradiation to the start of paclitaxel in responding patients was 94 weeks, whereas in patients with stable disease it was 68 weeks, and in patients whose disease progressed it was 46 weeks. Eighty-eight percent of the 105 cycles of paclitaxel were administered at a dose of 250 mg/m2 or higher. Granulocytopenia was brief and noncumulative, with grades 3 and 4 experienced by 5 and 3 patients, respectively. G-CSF was used for a median of 7 (range, 2-14) days/cycle. Anemia was mild, with G3 noted in 3 patients, and thrombocytopenia was not significant. Infections and musculoskeletal pain were mild and infrequent. Sensory (14 patients G1 or G2 and 2 patients G3) and motor (4 patients G1 or G2 and 1 patient G3) neurotoxicity was noted. There was no significant cardiovascular toxicity. Paclitaxel is active in patients with squamous cell cancer of the cervix and is well tolerated at this dose schedule with G-CSF support.

The results of a phase II randomized trial comparing 5-fluorouracil and 5-fluorouracil plus alpha-interferon: observations on the design of clinical trials for androgen-independent prostate cancer.

The therapeutic benefit of chemotherapy in androgen independent prostate cancer is limited. 5-Fluorouracil has been reported to have modest antitumor activity in androgen independent prostate cancer. Although alpha-interferon is inactive as a single agent in prostate cancer, preclinical data indicate that it increases the in vitro cytotoxicity of 5-fluorouracil against a variety of malignant cells. We evaluated the relative antitumor activity and tolerance of 5-fluorouracil versus 5-fluorouracil plus alpha-interferon in 50 patients with histologically confirmed metastatic adenocarcinoma of the prostate. These patients had progressive disease in the presence of castrate levels of testosterone. A prospective randomized phase II open labeled trial was performed because of the difficulty in measuring responses in patients with metastatic prostate cancer. Of 23 patients treated with 5-fluorouracil alone and 28 treated with 5-fluorouracil plus alpha-interferon 17 and 23, respectively, were evaluable for response and toxicity, and 5 and 5, respectively, were evaluable for toxicity only. Only 2 of 17 (11.7%) and 4 of 23 (17%) patients, respectively, showed a greater than 50% decrease in serum prostate specific antigen (no significant difference). There was no difference in duration of response or duration of survival between the 2 groups (mean duration of response 8.64 and 6.17 weeks, respectively, and mean duration of survival 33.70 and 38.65 weeks, respectively). Both regimens caused significant morbidity (mucositis and neurotoxicity) and 3 treatment related deaths at the high 5-fluorouracil doses. 5-Fluorouracil alone and with alpha-interferon at the doses used have minimal antitumor activity against androgen independent prostate cancer and, therefore, should not be tested further in these patients. Androgen independent prostate cancer selected using our criteria is a rapidly progressive disease, and these patients are an ideal target population for phase II studies.

Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.

BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. RESULTS: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4 had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.