FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials.

BACKGROUND: FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. PATIENTS AND METHODS: A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. RESULTS: Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Köhne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group {propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59-0.94], P = 0.013}. This association was significant also in the multivariable model (P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56-0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS (P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81-2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68-1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. CONCLUSIONS: Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. TRIALS' NUMBERS: NCT01219920 and NCT00719797.

Efficacy and feasibility of induction chemotherapy and radiotherapy plus cetuximab in head and neck cancer.

BACKGROUND: To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab. PATIENTS AND METHODS: Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity. RESULTS: Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase. CONCLUSION: Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.

Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial.

AIMS: Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single-stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients' compliance compared with standard-dose cisplatin with similar outcome results. MATERIALS AND METHODS: Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m(2)) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck. RESULTS: Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively. CONCLUSIONS: Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in 'unfit' patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded.