Phase II evaluation of suramin in advanced renal cell carcinoma. A Southwest Oncology Group study.

Twenty-two eligible patients with advanced renal carcinoma were treated with suramin utilizing a fixed dose regimen. Therapy was reasonably well tolerated with 3 of 22 patients (14%) developing grade 4 toxicity and 11 of 22 patients (50%) having a maximum toxicity of grade 3. There were no responders; median survival was 10 months. Suramin is not an active agent in advanced renal carcinoma.

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999.

BACKGROUND: After standard therapy for advanced head and neck carcinoma, 5-year survival rate is less than 50%. Our purpose was to develop a new treatment for advanced head and neck carcinoma by using preoperative chemotherapy. Long term efficacy and toxicity of induction paclitaxel and carboplatin is reported here. METHODS: Between 1994 and 1999, 62 consecutive patients with newly diagnosed head and neck carcinoma were treated with paclitaxel and carboplatin induction chemotherapy. Chemotherapy was administered every 21 days with 3 courses of paclitaxel (150-265 mg/m(2)) and carboplatin at a dose calculated using the Calvert formula area under the curve of 7.5. Patients who achieved complete or partial response at the primary received definitive radiation to the primary tumor and those with lymph node disease received neck dissection followed by radiation to the regional lymph nodes. Nonresponders received standard resection of primary tumor and draining lymph node basin followed by radiation. RESULTS: Sixty-two consecutive patients were treated. Seventy-four percent had Stage IV (according to the 5th edition of American Joint Committee on Cancer Staging manual) disease. The median duration of follow-up from initiation of chemotherapy was 64 weeks (range, 1-272 weeks). Overall complete plus partial response rate was 41 of 62 (66%). Responses were observed at all anatomic sites: oropharynx 20 of 33 (61%); hypopharynx 8 of 12 (67%); and larynx 13 of 17 (76%). Kaplan-Meier estimates of overall survival (OS), at 230 weeks, were significantly better in Stage IV oropharynx/hypopharynx responders than nonresponders (55% vs. 27%; P = 0.04). Of the variables evaluated in multivariate models, response at the primary tumor and lymph nodes were associated with improved disease free survival and OS. Organ preservation was achieved in 28 of 62 (45%) of patients at all anatomic sites: oropharynx 39%, hypopharynx 42%, larynx 59%. Seventeen of 28 (61%) patients had their primary organ site preserved for a mean duration of 78 weeks (range, 13-238 weeks). CONCLUSIONS: Induction paclitaxel and carboplatin was well tolerated. The response rate was encouraging considering most patients were Stage IV. Chemotherapy response identified a group with improved prognosis. Organ preservation was possible at all anatomic sites.

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.

A multicenter, double-blind, randomized comparison of oral ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with highly emetogenic chemotherapy. S3AA3012 Study Group.

The objectives of this study were to compare the efficacy and safety of orally administered ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with high-dose cisplatin-based chemotherapy (cisplatin > or = 50 mg/m2). This was a randomized, parallel-group, double-blind study conducted in North America. It was planned that all patients would receive one of the following orally administered ondansetron treatments 30 min before starting cisplatin dosing (administered over < or = 3 h): 8 mg b.i.d. with 8 h between doses (124 patients), 24 mg q.d. (116 patients), and 32 mg q.d. (117 patients). Use of prophylactic corticosteroids was not permitted. During the 24-h study period, the highest complete response rate (no emesis, rescue antiemetic therapy, or withdrawal) occurred in patients who received ondansetron 24 mg q.d.: 76/115 or 66%, as against 68/124 (55%) after ondansetron 8 mg b.i.d. and 64/117 (55%) after ondansetron 32 mg q.d. Complete control of nausea (no nausea, no rescue, no withdrawal) occurred in more patients in the ondansetron 24 mg q.d. group (64/114, 56%) than in the ondansetron 8 mg b.i.d. group (43/121, 36%) or in the ondansetron 32 mg group (55/117, 50%). These results demonstrate that following highly emetogenic cisplatin-based chemotherapy (> or =2 50 mg/m2), oral ondansetron 24 mg q.d. is more effective than 8 mg b.i.d. for overall control of nausea, and at least as effective if not more effective in the control of acute vomiting than 8 mg b.i.d. or 32 mg q.d. Ondansetron 24 mg q.d. was well tolerated, and no new or unexpected adverse events were identified.

Vinblastine and methotrexate for advanced bladder cancer.

Fifty-seven patients with advanced measurable urothelial tract cancer, 52 of whom had an adequate trial, were treated weekly with 3 to 4 mg. per m.2 vinblastine and 30 to 40 mg. per m.2 methotrexate. Of 3 patients with unidimensional parameters 2 showed improvement lasting 16 and 27 months, which was documented by serial cystoscopic examinations. An additional 2 patients had measurable disease that could have been encompassed in a preoperative radiotherapy field. Both patients are free of disease at more than 12 and 14 months, respectively. Of the 47 patients with bidimensionally measurable parameters 19 (40 per cent) achieved a complete or partial remission lasting a median of 8 months, with a range of 1 to 24 months. Of 25 patients with intra-abdominal or pelvic disease 7 achieved a complete or partial remission and 5 also had a minor remission. Of note, 18 of 38 patients who had received no prior chemotherapy achieved a remission versus 1 of 9 who had been treated previously (p equals 0.06). Responders frequently obtained another remission with subsequent chemotherapy (4 of 9 versus 0 of 16, p equals 0.03). Responders lived 14 months versus 8 months for nonresponders (p equals 0.02). Four responders had brain metastases compared to none of 28 nonresponders. The combination of vinblastine and methotrexate is a well tolerated, effective outpatient regimen for patients with urothelial tract cancers.

Phase II trial of 4'epi-adriamycin for advanced hypernephroma.

4'Epi-adriamycin in doses of 85-110 mg/m2 I.V. Q3W was given to 20 patients with advanced bidimensionally measurable hypernephroma. Forty-five doses were administered, with 10 patients receiving 3-7 doses. Myelosuppression (WBC nadir 2600 cells/mm3, range 1000-3400) occurred in 63% and thrombocytopenia in 16% of cases. There was no objective response in 19 adequately treated cases.

Intravenous cisplatin for superficial bladder tumors.

Cisplatin, 1.25 mg/kg IV QM, was administered to 15 patients with recurrent flat carcinoma in situ and/or bladder tumors confined to the mucosa and lamina propria. All patients had a history of multiple transurethral resection and 4 had received prior irradiation and two prior intravesical thiophosphoramide. Response was evaluated by urinary cytologic findings, cystoscopy and biopsy. Of 14 adequately treated cases, four (28%) had disappearance of all visible lesions, cystoscopically, for a median of eight months (range, 8-18), and six exhibited transiently a greater than 50% decrease in the number of tumors. However, no patient demonstrated a complete remission--all had persistently positive urinary cytologies. Nausea and vomiting, even at this dose level, was significant and at times, severe. Cisplatin, in the dose and schedule used, was found to be ineffective in controlling low-stage bladder tumors.

Intravesical cisplatin for superficial bladder tumors.

Cisplatin, 50-150 mg in a maximum concentration of 1 mg/ml, was administered intravesically each week to 24 patients with multiple, recurrent carcinoma in situ and/or bladder tumors confined to the mucosa and lamina propria. All patients had a history of multiple transurethral resections and four had received prior chemotherapy. Response was evaluated by urinary cytology, cystoscopy, and biopsy. In a total of 237 weekly doses, toxicities included mild dysuria, pruritus, rash and in one patient, acute anaphylaxis. Only three (13%) patients were classified as achieving complete remission. Cisplatin, in the dose and schedule employed, is ineffective in controlling superficial bladder cancer.