A Pilot Trial of Combination Cisplatin, 5-Fluorouracil and Interferon-α in the Treatment of Advanced Esophageal Carcinoma

Abstract

Background/Objectives: Based on the synergistic effect between cisplatin and 5-fluorouracil (5-FU), and between 5-FU and interferon-α, we conducted a trial to assess the response rate and toxicity of the combination of cisplatin, 5-FU and interferon-α in patients with advanced esophageal cancer. Methods: Patients with locally advanced or metastatic squamous cell or adenocarcinoma of the esophagus were eligible. No prior chemotherapy or interferon were allowed. Patients received cisplatin 80 mg/m² on day 1, 5-FU 750 mg/m²/day by continuous intravenous infusion for 5 days, and interferon-α 5 × 10⁶ units/m²/day by subcutaneous injection on days 1–5 of each cycle. Cycles were repeated every 21 days for a total of 6 cycles. Results: Forty patients were enrolled. Median age was 57.5 years (range 30–70). 33 had squamous carcinoma and 7 adenocarcinoma; 15 were male; the locoregional metastatic ratio was 1:39; median ECOG performance status was 2 (range 1–3). Grade 3–4 toxicities were: leukopenia (9 cases), thrombocytopenia (4), electrolyte imbalance (11), febrile neutropenia (11), vomitting (5), diarrhea (4), and mucositis (11). There were 3 early deaths, most probably related to therapy. Five patients (13%) achieved a complete response and 17 (42%) achieved a partial response, yielding an overall response rate of 55%. Response rates for squamous and adeno histology were 61% and 29%, respectively. Median survival was 6.4 months. Conclusion: The combination of cisplatin, 5-FU and interferon-α produces a high response rate in advanced squamous cell esophageal carcinoma, but with considerable toxicity. A modified combination of the above agents is presently being evaluated at our institution.

Effects of Dexamethasone, All-Trans Retinoic Acid, Vitamin D₃ and Interferon-α on FO Myeloma Cells

“…It is well known that interferon-α has an antitumoral effect in some malignant diseases [18]. In this study, the effect of interferon-α on myeloma cell count may be the result of induction of apoptosis and antiproliferative effects of interferon-α [16].…”

Effects of Cisplatin, 5-Fluorouracil, and Radiation on Cell Cycle Regulation and Apoptosis in the Hypopharyngeal Carcinoma Cell Line

“…The combined regimen of cisplatin and 5-FU is mainly used for malignant head and neck tumors that include hypopharyngeal cancer and esophageal carcinoma [1,2]. The activity of cisplatin is thought to be based on the formation of inter-and intrastrand DNA cross-links [3].…”

Cancer and Pregnancy Share Similar Mechanisms of Immunological Escape

“…During immunization with immune cells, the patient's own lymphocytes pre-sensitized against TAA in vitro, combined with sensitized Th1 cytokines (IL-2, IL-12 and IFN-␥ ) [28] or bacterial adjuvant [32] , become capable of killing cancer cells or inducing their apoptosis. There are also trials which combine the therapeutic effect of chemotherapy with Th1 cytokines [33] . Techniques of active immunotherapy increase the function of cytotoxic cells and shift the cytokine balance towards Th1 activity, which is achieved by three main approaches: (1) blocking tolerance to self-antigens (TAA) using monoclonal antibodies against CTLA-4 or by depletion of CD4+/CD25+ regulatory cells, (2) enhancement of TAA immunogenicity by pulsing dendritic cells with isolated tumor TAAs or TAA peptides and (3) increasing immunogenicity of isolated TAA by combining them with bacterium-derived adjuvant [28] .…”