Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study.

PURPOSE: According to one of the most recent key scientific questions concerning the use of biomarkers in clinical trials, we investigated whether node-negative breast cancer patients, defined as high-risk cases on the basis of tumor cell proliferation, could benefit from cyclophosphamide, methotrexate, and fluorouracil (CMF) adjuvant therapy. PATIENTS AND METHODS: Two hundred eighty-one patients with negative nodes and rapidly proliferating tumors, defined according to thymidine labeling index (TLI), were randomized to receive six cycles of CMF or no further treatment after surgery +/- radiotherapy. RESULTS: The 5-year disease-free survival (DFS) was 83% for patients treated with CMF compared with 72% in the control group (P: =.028). Adjuvant treatment reduced both locoregional and distant metastases. When clinical outcome was analyzed in cell kinetic subgroups characterized according to tertile criteria, compared with patients in the control arm, 5-year DFS was significantly higher after adjuvant CMF in patients with TLI values in the second (78% v 88%, respectively; P: =.037) and third tertiles (58% v 78%, respectively; P: =.024). CONCLUSION: The results from this randomized clinical study indicate that patients with node-negative, rapidly proliferating tumors significantly benefit from adjuvant CMF.

Cell proliferation as a predictor of response to chemotherapy in metastatic breast cancer: a prospective study.

Many biologic prognostic markers are available for patients with breast cancer, and considerable interest has been devoted to confirm preliminary evidence of their role as indicators of treatment response. It remains to be assessed whether such markers are predictors of response only to first-line or also to successive therapies. Proliferative activity, defined by the 3H-thymidine labeling index (TLI), was determined on the primary lesion from 76 patients at time of first diagnosis. At relapse, patients underwent chemotherapy as absolute (48 cases) or relative (28 cases) first-line treatment, and their clinical response was analyzed in relation to the TLI of the primary lesion. The objective clinical response was significantly higher for rapidly (47%; CL, 33-61%) than for slowly proliferating tumors (15%; CL, 1-29%). These findings held true also when adjusted for metastatic site, previous treatment, chemotherapy regimen administered, and hormone receptor status. However, the direct relation between cell proliferation and benefit from chemotherapy held true only when such a treatment was used as an absolute first-line approach. Cell proliferation of primary lesions represents a consistent indicator of response to chemotherapy over time. Previously administered regimens, at least hormone therapy, could alter the proliferation-related chemosensitivity profile of individual tumors.

Combination chemotherapy in advanced ovarian carcinoma.

Ovarian carcinoma is the fifth most common cause of death among women in western countries. It is often diagnosed in an advanced stage (FIGO Stage III and IV) and requires effective chemotherapy as first-line treatment. The advent of cis-platin combined with adriamycin and cyclophosphamide has remarkably increased the response rate in advanced disease. The authors report 31 cases of epithelial ovarian neoplasia, without prior chemotherapy, treated with cis-platin, adriamycin and cyclophosphamide (PAC I). Of the 30 evaluable patients, 15 had clinical complete remissions (cCR = 50%), 10 clinical partial remissions (cPR = 33%) and 5 no response (NR = 17%). The total response (cCR + cPR) was equal to 83%. Twelve of the 15 patients in cCR underwent second-look laparotomy; in 8 of these cases, histologic and cytologic confirmation of CR was obtained. PAC I was found to be a highly effective therapeutic regimen with moderate toxicity. The individual toxicity reported was gastroenteric (nausea and vomiting), but transitory. No chronic toxic side-effects from cisplatin or adriamycin were noted. However, more definitive results must be obtained to verify its impact on the prolongation of survival.