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Background: Cases of severe gastrointestinal toxicity were monitored prospectively during NSABP C-07, a randomized clinical trial of adjuvant therapy for patients with stage II/III colon cancer., Methods: Patients were treated with weekly bolus 5-fluorouracil (5-FU) and leucovorin (FL; "Roswell Park Regimen") or the same regimen plus oxaliplatin (FLOX)., Results: Of 1857 patients, 79 (4.3%) developed a syndrome of bowel wall injury (BWI, small or large) characterized by hospitalization for the management of severe diarrhea or dehydration and radiographic or endoscopic evidence of bowel wall thickening or ulceration. Fifty-one (64.6%) of these adverse events occurred in patients treated with FLOX and 28 (35.4%) in those treated with FL (P < .01). Enteric sepsis (ES), characterized by grade 3 or greater diarrhea and grade 4 neutropenia with or without proven bacteremia occurred in 22 patients treated with FLOX, versus 8 in those treated with FL (P = .01). Patients >60 years were at higher risk for BWI after treatment with FLOX (6.7%) versus treatment with FL (2.9%, P < .01). Female patients had a higher incidence of BWI with FLOX (9.1%) than with FL (3.9%, P < .01). Severe gastrointestinal toxicity usually occurred during the third or fourth week on the first cycle of therapy, required hospitalization, and was managed with fluids, antidiarrheals, and antibiotics. There were 5 deaths (0.3%) due to enteropathy, 2 related to ES and 3 related to both BWI and ES. Seventy-one percent of patients resumed treatment with FL after recovery., Conclusions: Patients treated with adjuvant FL should be closely monitored for diarrhea and aggressively managed, especially if oxaliplatin has been added to the regimen. Society.

A phase II trial of CI-958 (NSC #635371), a new benzothiopyranoindazole was performed in patients with hormone refractory prostate carcinoma using prostate specific antigen (PSA) levels for response assessment. Twenty-two patients were entered on this study and twenty one were eligible. Toxicity consisted mainly of granulocytopenia (71% grade 3 or 4), but there were no significant infections. Two patients were removed from study due to asymptomatic decreases in cardiac ejection fraction. Of 21 evaluable patients, there were four responders (19%, CI 0-35%).

Purpose: Several multicomponent regimens have been reported to be useful in advanced androgen-independent prostate cancer. We used a randomized phase II design to evaluate and compare two such regimens. Patients were accrued primarily in the community setting., Patients and Methods: Patients with progressive, androgen-independent prostate cancer were randomly assigned to one of two treatments: either ketoconazole/doxorubicin alternating with vinblastine/estramustine (KA/VE) or paclitaxel, estramustine, and oral etoposide (TEE). Patients were prospectively stratified on the basis of disease volume. The primary end points were response and overall survival time., Results: A total of 75 patients were registered; 71 are included in the analysis. By the criterion of an 80% prostate-specific antigen reduction maintained for at least 8 weeks, 11 (30%) of 37 patients in the TEE arm responded, whereas 11 (32%) of 34 assigned to KA/VE responded. Median survival was 16.9 months (95% confidence interval [CI], 10.5 to 21.2 months) in the TEE arm and 23.4 months (95% CI, 12.9 to 30.6 months) for patients treated with KA/VE. Many patients (24%) failed to complete at least 6 weeks of therapy, including five (8%) treatment-related early deaths., Conclusion: Each of these regimens produced clinically significant responses, and the observed median survival (18.9 months for all 71 patients) compares favorably with previously published results, especially in the community setting. Nonetheless, it is apparent that these first-generation regimens must be applied judiciously, and thus we view efforts at better patient selection and the development of more tolerable therapies as higher priorities than carrying either of these regimens to phase III evaluation in the cooperative group setting.

Background: Chemotherapeutic treatments containing topoisomerase I inhibitors have shown antitumor activity against a number of solid tumors. Responses have been seen in Phase I trials using topotecan in ovarian, lung, and esophageal cancer. A phase II trial using continuous infusion topotecan was completed to assess activity in esophagus cancer., Methods: Forty-five eligible patients with locally-advanced or metastatic squamous cell carcinoma or adenocarcinoma of the esophagus received a regimen consisting of 24-hour continuous infusion topotecan at 1.5 mg/m2/day on Days 1, 8, 15, 22 (of 42-day cycle). Patients continued on treatment until evidence of disease progression or unacceptable toxicity., Results: Partial response was demonstrated in 1 patient (2% confirmed response rate). Thirty-six patients progressed during the first cycle of treatment. The median survival was 3 months, and the median progression-free survival was 1 month. Toxicity was mild with only one Grade 4 toxicity reported., Conclusions: This phase II trial indicates no significant anti-neoplastic activity for topotecan administered in the dose and schedule to patients with squamous cell or adenocarcinoma of the esophagus.

We evaluated 9-aminocamptothecin (9-AC) in patients with metastatic or locally recurrent breast cancer who were no longer responsive to standard therapy. Patients were treated with 9-AC with a 72-hr continuous infusion given at a dose of 45 micrograms/m2/hr every 2 weeks. Granulocyte colony-stimulating factor 5 micrograms/kg was given subcutaneously for 7-10 days after completion of the treatment. Eighteen patients were treated, with all patients assessable for toxicity and 15 patients assessable for response. There were two partial responses seen in the 15 patients lasting 3.5 and 5 months, respectively. The major toxicity seen was myelosuppression, with 12 patients having grade 3 or greater granulocytopenia with four episodes of significant infectious complications. In addition, significant thrombocytopenia was seen in 14 patients. The other complications commonly seen were nausea and vomiting and alopecia. 9-AC given as a 3-day continuous infusion has limited activity in previously treated metastatic and locally recurrent breast cancer.

The combination of 5-fluorouracil and cisplatin has shown encouraging results in single institution pilot studies in colorectal carcinoma. This phase II SWOG study was undertaken to further evaluate this treatment. Cisplatin was administered at a dose of 60 mg/M2 IV day 1, repeated every 21 days. 5-FU was given at a dose of 15 mg/Kg IV days 1, 8, and 15, with cycles repeated every 21 days. Among 47 eligible patients there were no complete responses and only three partial responses for an overall response rate of 6% with a 95% confidence interval of 1% to 18%. Seventeen patients (36%) had stable disease/no response and 22 (47%) progressed. Five patients (10%) had no evaluation and were assumed to have had no response, or were early deaths. Median survival was 9.1 months. Significant hematologic toxicity was seen with grade 3 leukopenia occurring in 11 patients. There were felt to be two deaths definitely related to treatment and two additional deaths possibly treatment related. The combination of 5-FU and cisplatin used in this dose and schedule is an ineffective and toxic regimen for treatment of colorectal carcinoma.

Interferon-alpha, interferon-beta, and interferon-gamma differ in their antiproliferative effects for several cell lines. Interferons were thus assessed for their activity in inhibiting proliferation of three renal cell carcinoma cell lines. The malignant epithelial phenotype of each of these cell lines was confirmed by electron microscopy, histology, karyotype and tumorigenicity. When compared on an anti-viral unit basis, naturally produced interferon-beta was more effective than natural interferon-alpha for all cell lines and clones. Proliferation of each of the cell lines was inhibited by interferon-gamma. In all cases, removal of interferons from culture media resulted in resumption of the rate of cell growth after a variable delay of 6-10 days. If the antiproliferative effects of interferons predominate in mediating tumor regression, clinical response may depend upon the type of interferon to which the tumor is exposed.