retinol-palmitate and Neoplasm-Metastasis

Based on the additive or synergistic antiproliferative effect of interferon and tamoxifen on breast cancer cell lines and on preclinical and clinical data on retinoids alone and in combination with antiestrogen or interferon, we designed a pilot phase II study to test the toxicity of simultaneous administration of interferon-beta (IFN-beta), retinoids (R), and tamoxifen (TAM) and the efficacy of this combination as salvage therapy in a group of patients with metastatic breast cancer (MBC). A total of 49 stage IV breast cancer patients, 11 pretreated with hormones, 26 with chemotherapy, and 12 with both, received 30 mg TAM and two dose levels of IFN-beta and retinyl palmitate. Among 49 evaluable patients, 27 achieved a clinical response (55%; 95% CI 41-69%), 10 had stable disease (20%), and in 12 (25%) the disease progressed. Toxicity with both dose levels was moderate and mainly hepatic. Median response duration, not statistically different in estrogen receptor-positive and negative patients, was 31.4 months (range 4.9-67). Median overall survival was 19.2 months (range 2-69). We have shown that long-term administration of TAM, IFN-beta, and retinyl palmitate is feasible with moderate toxicity. We have also demonstrated that this regimen is active in pretreated MBC patients and that responses are not influenced by receptor status.

Topics: Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Diterpenes; Drug Synergism; Female; Follow-Up Studies; Humans; Interferon-beta; Middle Aged; Neoplasm Metastasis; Pilot Projects; Retinyl Esters; Tamoxifen; Vitamin A

This article summarizes the histories of six patients with different solid tumors treated with a new strategy based on tumor burden reduction and immune evasion as potential targets. All six patients were at a high risk of relapse and were likely to have a minimal residual disease following conventional therapy: biochemical recurrence (BCR) following radical prostatectomy (RP) (two prostate cancers patients), removal of distant metastases (one colorectal and one breast cancer), and complete response (CR) of distant metastases to conventional therapy (one breast cancer and one esophageal-gastric junction cancer). Four of the patients, two after RP and BCR, one after removal of a single pulmonary metastasis from breast cancer, and one after CR to chemotherapy of peritoneal metastases and ascites from an esophageal-gastric junction primary cancer, regularly received cycles of a new drug schedule with the aim of inhibiting immune suppression (IT). In these four patients, preliminary laboratory tests of peripheral blood suggested an interleukin (IL)-2/IL-12 mediated stimulation of cellular immune response with a concomitant decrease in vascular endothelial growth factor (VEGF) immune suppression. The fifth case was a breast cancer patient with distant metastases in CR, while receiving beta-interferon and interleukin-2 in addition to conventional hormone therapy. To date, all five patients are alive and doing well and they have been unexpectedly disease-free for 201 and 78 months following BCR, 28 months following the removal of a single pulmonary metastases, 32 months following CR to chemotherapy of peritoneal metastases and ascites, and 140 months following diagnosis of multiple bone metastases, respectively. The sixth patient, who had colorectal cancer and multiple synchronous liver metastases and underwent nine surgical interventions for metastatic disease, although not disease-free, is doing well 98 months after primary surgery. Our six cases reports can be interpreted with the hypothesis that immune manipulation and/or a concomitant low tumor burden favored their clinical outcome.

Topics: Adult; Aged; alpha-Tocopherol; Antineoplastic Agents; Breast Neoplasms; Celecoxib; Colonic Neoplasms; Cyclooxygenase 2 Inhibitors; Cyclophosphamide; Dexamethasone; Diterpenes; Female; Humans; Immunosuppressive Agents; Interleukins; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Retinyl Esters; Tumor Burden; Tumor Escape; Vitamin A; Vitamins