Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer.

PURPOSE: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. METHODS AND MATERIALS: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m(2)/week for 6 weeks), and continuous infusion 5-FU (200 mg/m(2)/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m(2)/week. Resection was performed 4-8 weeks after the completion of chemoradiation. RESULTS: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). CONCLUSIONS: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

Lapatinib and gemcitabine for metastatic pancreatic cancer. A phase II study.

PURPOSE: To determine the overall survival for patients with metastatic pancreatic cancer treated with lapatinib and gemcitabine. MATERIALS AND METHODS: Patients with metastatic pancreatic cancer received lapatinib, 1,500 mg/d, and Gemcitabine, 1 g/m(2)/wk for 3 weeks followed by 1 week off, until disease progression. This multicenter phase II study was planned to enter 125 patients to evaluate whether the treatment regimen could achieve a 1-year survival of 30% and a median survival of 7 months. An additional subset of 20 patients were to receive 2 months of single agent lapatinib followed by lapatinib and gemcitabine. RESULTS: At a planned 6 month analysis, the Brown University Oncology Group Data Safety Monitoring Board terminated accrual after 29 patients because of futility analysis. The median survival was 4 months (95% confidence interval, 3.0-5.0 months). Three of the 29 (10%) patients had a partial response. The 4 patients who received single agent lapatinib all progressed at 1 month. CONCLUSION: Lapatinib is not effective in pancreatic cancer. Evaluation of HER2 inhibitors in pancreatic cancer is not warranted.

Acute myelogenous leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease with outcomes dependent upon several factors, including patient age, karyotype, mutational status, and comorbid conditions. For younger patients, approximately 60% to 80% achieve complete remission with standard therapy involving cytarabine and an anthracycline. However, only 20% to 30% have long-term disease-free survival. For adults older than 60 years of age, only 40% to 55% achieve a complete remission, with dismal long-term survival rates. Unfortunately, the median age at diagnosis for AML is 70 years. Significant advances in our understanding of the molecular biology of AML have led to newer therapies that specifically target molecular abnormalities. Examples of such therapies include the immunoconjugate gemtuzumab ozogamicin, FMS-like tyrosine kinase 3 inhibitors, farnesyl transferase inhibitors, histone deacetylase inhibitors, DNA hypomethylating agents, multidrug-resistance inhibitors, BCL-2 inhibitors, antiangiogenesis agents, and various nucleoside analogs. This review summarizes the standard treatments for AML and discusses the role of novel therapies.