Fifty-six untreated patients with inoperable squamous cell carcinoma of the head and neck were treated with carboplatin 70 mg/m2 i.v. daily on days 1-5 and 29-33 in combination with simultaneous conventional radiation up to a target volume dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons, 21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two courses of carboplatin. Patients who showed pCR after surgery received no further radiotherapy. In all other patients radiotherapy was continued using a shrinking field technique up to a target absorbed dose of 70-74 Gy. Combined modality induced 66% complete remission (CR) and an overall response rate of 98%. After completion of the whole treatment program (combined modality +/- surgery) 53 (94%) of the 56 patients were disease free. The median survival for all patients is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression was the most frequent toxicity, but rarely was severe; leukopenia and thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and ototoxicity were not seen. The addition of carboplatin did not increase the rate of surgical complication over that expected for preoperative radiotherapy. Two patients died of pulmonary embolism after surgery. Combined modality with carboplatin and simultaneous radiation is a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck.

362 evaluable node-positive patients with stage II breast cancer were randomized, receiving either 6 cycles of conventional CMF or 6 cycles of the combination of cyclophosphamide (500 mg/m²), mitoxantrone (Novantrone 10 mg/ m²), and fluorouracil (500 mg/m²; CNF). After a median follow-up of 51 months, 64 (36%) patients relapsed in the CMF group and 60 (33%) in the CNF group (p = 0.8276). By Cox multivariate analysis, tumor size, menopausal status and number of involved nodes were retained as independently significant variables. Toxicities were remarkably similar in both groups. It appears that after a median follow-up of 51 months there is no significant difference in relapse-free survival between node-positive patients with breast cancer who received either 6 cycles of the conventional CMF or the CNF combination as adjuvant treatment.

From 1987 to 1991, 100 evaluable patients with advanced head and neck carcinomas (T2–4, N0–3) were treated with radiotherapy and simultaneous carboplatin. Tumors were located in the oral cavity in 33 patients, oropharynx in 8 patients, and hypopharynx in 7 pateints. four patients had a tumor of the epipharynx, 3 of the larynx, and 45 had involvement of two or more compartments. radiotherapy was performed in a fractionation of 5 × 2 Gy/week up to a dose of 50 Gy. Carboplatin was administered in a dose of 60 or 70 mg/m² from days 1–5 qand 20–33. After a 2-week interval, tumor in invlution was evaluated and a decision was made on the patients’ operability. In cases of inoperability, radiotherapy was continued up to a dose of 70–74 Gy. thirty patients underwent surgery after 50 Gy. Eight patients showed a histologically complete remission (CR), 7 showed microscopic residual tumor, and 15 showed macroscopic tumor. Seventy patients were treated with radiotherapy and concomitant carboplatin only. Thirty-nine of them achieved a CR and 30 a partial remission (PR). The residual tumor was operable in 8 of the latter patients. Only a minor response was achieved in the remaining patient At the end of the treatment 77 patients achieved a CR with this combined modality. From 1990 to 1992, 20 patients with locally advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 × 1.6 Gy/day, 5 days per week; total dose, 64–67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m², days 1–5 and 29–33) in a pilot study. Fifteen patients had T4 and 5 had T3 tumors. Six weeks after the end of treatment, 16 patients (80%) had CR, and PR was seen in the other 4 patients (20%). Overall and disease-free survival at 1 year was 82 and 81%, respectively. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial CR rate 80% is encouraging. Because of the results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy with carboplatin or hyerfractionated accelerated irradiation with carboplatin. Results will be forthcoming.

The present randomized phase III trial was designed to detect a 15% benefit in relapse-free survival (RFS) or overall survival (OS) from the incorporation of adjuvant tamoxifen to the combination of CNF [cyclophosphamide, 500 mg/m2; mitoxantrone (Novantrone), 10 mg/m2; fluorouracil, 500 mg/m2 chemotherapy and ovarian ablation in premenopausal patients with node-positive breast cancer and conversely from the incorporation of CNF chemotherapy to adjuvant tamoxifen in node-positive postmenopausal patients. From April 1992 until March 1998, 456 patients with operable breast cancer and one to nine infiltrated axillary nodes entered the study. Premenopausal patients were treated with six cycles of CNF chemotherapy followed by ovarian ablation with monthly injections of triptoreline 3.75 mg for 1 year (Group A, 84 patients) or the same treatment followed by 5 years of tamoxifen (Group B, 92 patients). Postmenopausal patients received 5 years of tamoxifen (Group C, 145 patients) or 6 cycles of CNF followed by 5 years of tamoxifen (Group D, 135 patients). Adjuvant radiation was administered to all patients with partial mastectomy. After a median follow-up period of 5 years, 125 patients (27%) relapsed and 79 (17%) died. The 5-year actuarial RFS for premenopausal patients was 65% in Group A and 68% in Group B (p = 0.86) and for postmenopausal patients 70% in Group C and 67% in Group D (p = 0.36). Also, the respective OS rates were 77% and 80% (p = 0.68) for premenopausal and 84% and 78% (p = 0.10) for postmenopausal patients. Severe toxicities were infrequently seen, with the exception of leukopenia (18%), among the 311 patients treated with CNF. In conclusion, the present study failed to demonstrate a 15% difference in RFS in favor of node-positive premenopausal patients treated with an additional 5 years of tamoxifen after CNF adjuvant chemotherapy and ovarian ablation. Similarly, six cycles of CNF preceding 5 years of tamoxifen did not translate to a 15% RFS benefit in node-positive postmenopausal patients.

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