ABSTRACT
PURPOSE: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS). RESULTS: One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46-0.87; P = 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53-0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times. CONCLUSIONS: Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Alum Compounds/administration & dosage , Antibodies, Monoclonal/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antibodies, Monoclonal, Murine-Derived , Cancer Vaccines/administration & dosage , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Double-Blind Method , Female , G(M3) Ganglioside/analogs & derivatives , G(M3) Ganglioside/immunology , G(M3) Ganglioside/metabolism , Humans , Kaplan-Meier Estimate , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Maintenance Chemotherapy , Male , Middle Aged , Neoplasm Staging , Placebos , Proportional Hazards Models , Treatment OutcomeABSTRACT
Introduction In Cuba, colorectal cancer (CRC) is the malignant neoplasm with the fourth-highest incidence and third-highest mortality. Over one-third of CRC patients exhibit metastatic disease at the time of diagnosis. Standard treatment for metastatic CRC is a 5-fluorouracil (5-FU) + Folinic Acid (FA) continuous infusion regimen. International studies have shown, however, that systemic therapy using oxaliplatin combined with 5-FU and FA (FOLFOX-4) improves results in terms of both tumor response and survival in patients with inoperable metastatic CRC. Objective Evaluate the FOLFOX-4 regimen as a first-line therapy for patients with inoperable metastatic CRC in Cuba. Methods FOLFOX-4 therapy was administered to 56 patients with metastatic CRC, in a treatment cycle repeated every 2 weeks for 6-8 cycles. Patients were followed up for a period of 2 years. Results Objective response was attained in 44.6% of patients, and complete response in 12.5%. Median duration of response and of progression-free survival was 9.6 and 8.9 months, respectively. Estimated survival at 2 years was 17% (95% CI: 6.89-26.8). The most frequent adverse events were nausea, vomiting, diarrhea and neutropenia, the majority grade 1-2, according to Common Terminology Criteria for Adverse Events (CTCAE) classification. Conclusions In patients studied, the FOLFOX-4 combination was shown to be an effective and well-tolerated therapeutic option for treating inoperable metastatic colorectal cancer.
