The prognosis of stage III breast cancer treated with postoperative radiotherapy and adriamycin-based chemotherapy with and without tamoxifen. Eight year follow-up results of a randomized trial.

Sixty-one patients with primary node positive stage III breast cancers were randomized to receive postoperative radiotherapy and doxorubicin-based chemotherapy (eight cycles of CAFt: cyclophosphamide, adriamycin, oral ftorafur) with or without tamoxifen as adjuvant treatment. The five-year overall survival for all patients was 49% (with tamoxifen 48% and without tamoxifen 50%) and disease-free survival 33% (with tamoxifen 27% and without 39%). Local control for all patients was only 64% despite the postoperative radiotherapy. There was no significant difference between these two treatment groups in overall and disease-free survival or local control. The prognosis of stage III breast cancer remains grim despite modern adjuvant therapy. In addition to more effective systemic treatment more effective local therapy is also needed in order to obtain satisfactory local control. The most important studies in stage III breast cancer with 5-year survival results are reviewed here.

Intermittent interferon and polychemotherapy in metastatic melanoma.

This study was conducted to evaluate the efficacy and the tolerability of a four-drug chemotherapy regimen combined with interferon alpha (IFN) in metastatic melanoma. Between March 1991 and August 1993, 55 patients with advanced melanoma were enrolled for the present multicentre phase II study. Forty-nine patients were eligible and evaluable for toxicity; 48 patients were evaluable for response. The treatment schedule consisted of a 5-day regimen of dacarbazine, vincristine, bleomycin and lomustine, plus 6 x 10(6) IU IFN alpha three times weekly subcutaneously for 2 weeks starting on day 8. The cycle was repeated on day 29. Among the 48 assessable patients, 16 objective responses were seen, yielding a response rate of 33% (95% confidence interval 20%-46%). Seven patients achieved a complete response (CR) of a median of 6+ months (range 1+ to 21+ months) and 9 patients achieved a partial response (PR) of a median of 9 months (range 4-13 months). The median overall survival was 12+ months (range 6+ to 23+ months) for the patients with CR and 15+ months (range 8-20 months) for the patients with PR. Even the survival of the 7 patients with stable disease was fairly long (median 12, range 7-17 months), appearing to be significantly longer than the survival of the 25 patients with progressive disease (median 5, range 1-24+ months). The treatment was moderately well tolerated, although all patients experienced some mild form of toxicity, mostly gastrointestinal symptoms, neurotoxicity and haematotoxicity. Grade 3-4 adverse effects were noted in 39% of the patients. No toxic deaths occurred. It can be concluded that the present regimen produces meaningful responses for patients with metastatic melanoma. A randomised study is needed to determine the effect on survival.

The combination of radiotherapy, adjuvant chemotherapy (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer. Long-term follow-up results of a randomised trial.

Two hundred patients with node positive stage II breast cancer were randomised to four groups after radical mastectomy and axillary evacuation: (1) Postoperative radiotherapy, (2) Adjuvant chemotherapy with eight courses of CAFt (cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-1 orally day 1-14) every fourth week, (3) Postoperative radiotherapy and adjuvant chemotherapy and (4) postoperative radiation, adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years. Thirty-two per cent of the patients discontinued treatment due to GI-toxicity, while 26% required dose reductions due to leukopenia. Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy. There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone (P = 0.05), which was highly significant in a multivariate Cox analysis (P = 0.004). No significant survival differences were seen. Tamoxifen had no clear overall effect but there were better relapse-free (P = 0.04) and overall (P = 0.004) survival with tamoxifen in estrogen receptor positive patients, while estrogen receptor negative patients had a somewhat poorer survival (P = 0.07) after tamoxifen. Local control was better (NS) after the combination (93%) radiotherapy and chemotherapy compared to either treatment alone (76% with radiotherapy and 74% with chemotherapy at 5 years).