Lenalidomide for second-line treatment of advanced hepatocellular cancer: a Brown University oncology group phase II study.

PURPOSE: To assess the activity and toxicity of lenalidomide for patients with advanced hepatocellular cancer (HCC) previously treated with sorafenib. MATERIALS AND METHODS: Patients with advanced HCC who progressed on or were intolerant to sorafenib were eligible. Patients received lenalidomide 25 mg orally for 1 to 21 days in a 28-day cycle until disease progression or unacceptable toxicities. RESULTS: Forty patients were enrolled and were classified according to the Child-Pugh score: 19 were Child-Pugh A, 16 patients were Child-Pugh B, and 5 were Child-Pugh C. Seventeen patients had extrahepatic disease. Grade 4 neutropenia occurred in 1 of 40 patients (2.5%). Grade 3 fatigue (n=3) and rash (n=4) were the most common nonhematologic toxicities attributable to lenalidomide. Six of 40 patients (15%) had a partial response. Two patients (5%) have not progressed at 36 and 32 months. The median progression-free survival was 3.6 months and the median overall survival was 7.6 months. CONCLUSIONS: Lenalidomide can be administered to patients with advanced HCC and hepatic dysfunction. Promising, and in a small percentage of patients, durable activity has been demonstrated. Investigations are needed to explore the mechanism of action of lenalidomide in HCC.

Lapatinib/gemcitabine and lapatinib/gemcitabine/oxaliplatin: a phase I study for advanced pancreaticobiliary cancer.

OBJECTIVE: To evaluate the safety/tolerability and potential antitumor activity of lapatinib, at dose ranges of 1000 to 1500 mg/d, in combination with gemcitabine and gemcitabine/oxaliplatin (GEMOX) in patients with advanced pancreaticobiliary cancer. MATERIALS AND METHODS: Patients with advanced pancreaticobiliary cancer were assigned to 1 of 4 cohorts of lapatinib administered once daily. Toxicities, response, and survival were assessed. RESULTS: Twenty-five patients were enrolled, 18 with pancreatic cancer and 7 with biliary cancer. Lapatinib, 1500 mg/d, was successfully administered with weekly gemcitabine. Dose limiting toxicities of nausea and anorexia occurred in 2 of 5 patients receiving 1500 mg/d lapatinib with GEMOX. The median survival of all patients was 11 months and the 1-year survival was 48%. CONCLUSION: Lapatinib, 1500 mg/d, can be administered with weekly gemcitabine. The maximum tolerated dose of lapatinib is 1000 mg/d with GEMOX. A phase II study of lapatinib and gemcitabine for metastatic pancreatic cancer will be initiated.

Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity.

PURPOSE: To determine the feasibility and toxicity of the addition of cetuximab with paclitaxel, carboplatin, and radiation for patients with esophagogastric cancer on a Phase II study. METHODS AND MATERIALS: Patients with locoregional esophageal and proximal gastric cancer without distant organ metastases were eligible. All patients received cetuximab, paclitaxel, and carboplatin weekly for 6 weeks with 50.4 Gy radiation. RESULTS: Sixty patients were enrolled, 57 with esophageal cancer and 3 with gastric cancer. Forty-eight had adenocarcinoma and 12 had squamous cell cancer. Fourteen of 60 patients (23%) had Grade 3 dermatologic toxicity consisting of a painful, pruritic acneiform rash on the face outside of the radiation field. The rates of Grades 3 and 4 esophagitis were 12% and 3%, respectively. Three patients had Grade 3/4 cetuximab hypersensitivity reactions and were not assessable for response. Forty of 57 patients (70%) had a complete clinical response after chemoradiation. CONCLUSION: Cetuximab can be safely administered with chemoradiation for esophageal cancer. Dermatologic toxicity and hypersensitivity reactions were associated with the addition of cetuximab. There was no increase in esophagitis or other radiation-enhanced toxicity.