Combination chemotherapy with cisplatin, methotrexate, bleomycin, and vincristine (CABO) in advanced squamous cell carcinoma of the head and neck

A combination of cisplatin, methotrexate, bleomycin, and vincristine (CABO) was assessed in advanced epidermoid head and neck cancer. Among 72 patients with recurrent or metastatic disease and measurable lesions, there were 9 complete and 27 partial responses for an overall response rate of 50%. These results were adversely affected by prior surgery plus prior radiotherapy. The median response duration was 28 weeks (16‐l00+) in complete responders and 16 weeks (6‐84) in partial responders. CABO was also administered to 56 patients with measurable, previously untreated, locoregional disease. In these patients, complete and partial response rates were 18% and 46%, respectively. Toxic effects were generally mild to moderate. In spite of its encouraging therapeutic efficacy, CABO is unlikely to be clearly superior to single‐agent chemotherapy, at least in recurrent or disseminated disease. Increased effectiveness of CABO given as initial treatment suggests that chemotherapy might play an effective adjuvant role in carefully selected patients. Copyright © 1984 American Cancer SocietySCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Combination chemotherapy with methotrexate, bleomycin, and vincristine with or without cisplatin in advanced squamous cell carcinoma of the head and neck

A total of 185 eligible patients with advanced inoperable squamous cell carcinoma of the head and neck were randomized into two groups; the cisplatin, methotrexate, bleomycin, and vincristine (CABO) group received cisplatin (50 mg/m2; day 4), methotrexate (40 mg/m2; days 1, 15), bleomycin (10 mg; days 1, 8, and 15), and vincristine (2 mg; days 1, 8, and 15) and the ABO group received methotrexate, bleomycin and vincristine in the same doses on days 1, 8, and 15. After three courses, patients in both arms received weekly methotrexate as maintenance therapy; those 34 patients with previously untreated locoregional disease went off the study because of subsequent locoregional treatment in form of radiotherapy—surgery. The complete response rate was 16% in patients receiving CABO, compared with 5% among patients given ABO. The corresponding overall response rates were 50% and 28%, respectively (P = 0.003). Among patients with recurrent or metastatic disease, progression was delayed in patients receiving CABO (median, 18 weeks) compared to those receiving ABO (median, 14 weeks) (P = 0.07), but there was no difference in survival time. Myelosuppression consisted mostly of leukopenia, which was seen in 67% of the CABO patients versus 47% in the other arm. Myelosuppression‐associated infection and hemorrhage led to death in two patients in the CABO treatment group and six patients in the ABO treatment group. Nausea and vomiting, mostly of grades 1 or 2, occurred in 93% of the patients given CABO and 44% of those receiving ABO. Other toxic effects—neuropathy, alopecia, stomatitis, constipation, fever/chills, diarrhea, cutaneous alterations, and renal impairment—occurred equally in the two treatment groups. This study underlines the role of cisplatin in head and neck cancer, although no impact on survival could be demonstrated. It also supports indirectly the superiority of combination chemotherapy over single‐agent treatment for this disease. Copyright © 1987 American Cancer SocietySCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Final 10-year results of the Breast International Group 2–98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer

Aim: Breast International Group (BIG) 2–98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2–98 and using a pooled analysis of three other randomised trials. Patients and methods: 2887 patients were randomly assigned in a 2 × 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. Results: After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81–1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76–1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.72–1.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 ⩾ 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63–1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57–1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01). Conclusion: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC