Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in metastatic colorectal cancer: results of the phase II North Central Cancer Treatment Group study N054C (Alliance).

BACKGROUND: Bevacizumab (BEV), a monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), is a standard component of medical therapy of metastatic colorectal cancer (mCRC). Activation of alternative angiogenesis pathways has been implicated in resistance to BEV. This phase II study examines the activity of combined vertical blockade of VEGF signaling with sorafenib and BEV as salvage therapy in patients with progressive disease (PD) on all standard therapy in mCRC. METHODS: mCRC patients with documented PD on standard therapy, received sorafenib (200 mg orally twice daily, days 1-5 and 8-12) and BEV (5 mg/kg intravenously, day 1) every 2 weeks. Primary endpoint was 3-month progression-free survival (PFS) rate and secondary endpoints were overall survival (OS), response rate (RR), safety, and feasibility. RESULTS: Of the 83 patients enrolled, 79 were evaluable. Of these, 42 (53%) were progression-free at 3 months. Median PFS was 3.5 months and median OS was 8.3 months. One patient had a partial response and 50 patients (63.3%) had at least one stable tumor assessment. Of 79 evaluable patients, 54 (68%) experienced grade 3/4 adverse events (AEs) at least possibly related to treatment. Most frequent grade 3/4 AEs were: fatigue (24.1%), hypertension (16.5%), elevated lipase (8.9%), hand-foot skin reaction (8.9%), diarrhea (7.6%), and proteinuria (7.6%). Reasons for treatment discontinuation were PD (72%), AEs (18%), patient refusal (8%), physician decision (1%), and death (1%). CONCLUSIONS: The combination of BEV and sorafenib as salvage therapy in heavily pretreated mCRC patients is tolerable and manageable, with evidence of promising activity. CLINICALTRIALSGOV IDENTIFIER: NCT00826540, URL:http://clinicaltrials.gov/ct2/show/NCT00826540.

A Pilot Study to Determine the Effect of an Educational DVD in Philippine Languages on Cancer Clinical Trial Participation among Filipinos in Hawai'i.

We conducted an experimental pilot study in an oncology clinic in Honolulu, Hawai'i to determine the effect of a culturally-tailored educational DVD on cancer clinical trial participation among Filipino cancer patients. Thirty-seven patients participated in the study, with 17 randomized into the control group (ie, usual education) and 20 into the intervention group (ie, usual education plus educational DVD). Participants completed pre- and post-educational questionnaires with items asking about understanding of several cancer topics, behavioral outcomes, and attitudes regarding several treatment and physician related topics. A Fisher's exact test was conducted to explore the association between enrollment into a clinical trial and group assignment. General linear models were created to determine significant differences between study groups in post-education response scores for each questionnaire item after controlling for age, gender, education, and pre-education response scores. Two participants from the control group and three participants from the intervention group enrolled into clinical trials. Results showed no significant association between clinical trial enrollment and study group assignment (P > .99). A significant difference was found between study groups on surety of joining the clinical trial suggested to them (P = .013). A multilingual educational DVD to supplement clinical trial education may positively influence Filipino cancer patients to move forward with the decision to join a cancer clinical trial. However, health literacy may serve as a major barrier to actual enrollment into the particular clinical trial available to a patient.

Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: North Central Cancer Treatment Group Trial N0745 (Alliance).

BACKGROUND: Angiogenesis has been a major target of novel drug development in hepatocellular carcinoma (HCC). It is hypothesized that the combination of two antiangiogenic agents, sorafenib and bevacizumab, will provide greater blockade of angiogenesis. OBJECTIVE: To determine the optimal dose, safety, and effectiveness of dual anti-angiogenic therapy with sorafenib and bevacizumab in patients with advanced HCC. PATIENTS AND METHODS: Patients with locally advanced or metastatic HCC not amenable for surgery or liver transplant were eligible. The phase I starting dose level was bevacizumab 1.25 mg/kg day 1 and 15 plus sorafenib 400 mg twice daily (BID) days 1-28. In the phase II portion, patients were randomized to receive bevacizumab and sorafenib at the maximum tolerated dose (MTD) or sorafenib 400 mg BID. RESULTS: Seventen patients were enrolled in the phase I component. Dose-limiting toxicities included grade 3 hand/foot skin reaction, fatigue, hypertension, alanine/aspartate aminotransferase increase, dehydration, hypophosphatemia, creatinine increase, hypoglycemia, nausea/vomiting, and grade 4 hyponatremia. Seven patients were enrolled in the phase II component at the MTD: sorafenib 200 mg BID days 1-28 and bevacizumab 2.5 mg/kg every other week; 57% (4/7) had grade 3 AEs at least possibly related to treatment. No responses were observed in the phase II portion. Estimated median time to progression and survival were 8.6 months (95% CI: 0.4-16.3) and 13.3 months (95% CI 4.4 - not estimable), respectively. CONCLUSIONS: The MTD of the combination is sorafenib 200 mg twice daily on days 1-28 plus bevacizumab 2.5 mg/kg on days 1 and 15 of a 28-day cycle. In the phase II portion of the trial, concerns regarding excessive toxicity, low efficacy, and slow enrollment led to discontinuation of the trial. (Clinical Trials ID: NCT00867321.).