Capecitabine and lapatinib for the first-line treatment of metastatic/recurrent head and neck squamous cell carcinoma.

BACKGROUND: The combination of cisplatin, 5-fluorouracil, and cetuximab is a standard treatment for patients with recurrent/metastatic head and neck cancer, with a high rate of toxicity. Identifying less toxic, equally effective regimens is imperative. Therefore, in the current study, the authors investigated first-line treatment with an all-oral regimen of capecitabine and lapatinib. METHODS: Patients were required to have incurable head and neck cancer of any primary site other than the nasopharynx, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine at a dose of 1000 mg/m(2) twice daily and lapatinib at a dose of 1250 mg daily. Capecitabine was administered for 14 days of each 21-day cycle for 4 cycles. Lapatinib was administered daily until disease progression. The primary outcome was overall survival. RESULTS: A total of 44 subjects were accrued between November 13, 2009 and April 29, 2014. Approximately 38.6% of the sample had an ECOG PS of 0, 52.3% had an ECOG PS of 1, and 9.1% had an ECOG PS of 2. Approximately 81.8% were male and the median age of the patients was 62 years. Prior attempts at curative treatment with chemotherapy had been used in 68.2% of patients (platinum was used in 55.8%). There was no grade 5 toxicity noted (toxicity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). The most common adverse events were diarrhea (18.2% of patients with grade 3) and rash (13.6% of patients with grade 3). The primary objective was met; the median overall survival was 10.7 months (90% confidence interval [90% CI], 8.7-12.9 months). The overall response rate was 25% (90% CI, 15%-38%). The median progression-free survival was 4.2 months (90% CI, 3.6-5.1 months). The results were not substantially different when subdivided by p16 status. Only 2 patients were positive for human epidermal growth factor receptor 2 by immunohistochemistry. CONCLUSIONS: The current study met its primary objective of survival comparable to the combination of cisplatin, 5-FU and cetuximab regimen, and the toxicity of this all-oral regimen was tolerable. Cancer 2016;122:2350-2355. © 2016 American Cancer Society.

Results of a Phase II Trial of Carboplatin, Pemetrexed, and Bevacizumab for the Treatment of Never or Former/Light Smoking Patients With Stage IV Non-Small Cell Lung Cancer.

INTRODUCTION: Bevacizumab- and pemetrexed-based therapies have demonstrated activity in patients with non-small-cell lung cancer (NSCLC) and nonsquamous histologic features. Patients with history of never or light smoking might derive greater benefit from these therapies. PATIENTS AND METHODS: The included patients had stage IIIB (malignant pleural effusion) or IV NSCLC with nonsquamous histologic features, adequate organ function, no contraindications to bevacizumab, and no previous cytotoxic therapy. The patients had also never smoked or had smoked ≤ 10 pack years and had quit ≥ 1 year before enrollment. The patients had received 4 cycles of carboplatin (area under the curve, 6), pemetrexed 500 mg/m(2), and bevacizumab 15 mg/kg. Patients without disease progression initiated maintenance therapy with pemetrexed and bevacizumab. A single-arm phase II trial with the primary endpoint of progression-free survival (PFS) was performed. The secondary endpoints were the objective response rate (ORR), overall survival (OS), and toxicity. RESULTS: From March 2010 to November 2013, 38 eligible patients were enrolled and treated in the trial. The most common histologic type was adenocarcinoma (97%). Most of the patients were women (66%) and never smokers (63%). The median PFS was 12.6 months (95% confidence interval [CI], 8.0-23.9 months). The ORR and OS were 47% (95% CI, 31%-64%) and 20.3 months (95% CI, 15.8-30.5 months). The grade 3 or 4 toxicities occurring at rate of ≥ 10% were neutropenia (18%), anemia (16%), fatigue (16%), hypertension (16%), and thrombocytopenia (11%). CONCLUSION: The combination of the carboplatin, pemetrexed, and bevacizumab demonstrated activity with acceptable toxicity in patients with a clinical history of never or light smoking.