isotretinoin and Colorectal-Neoplasms

We have previously shown that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (13-cis-RA) improved lymphocyte and natural killer (NK) cell count of patients with advanced tumors showing a clinical benefit from chemotherapy. The primary endpoint of this study was to ask whether IL-2 and 13-cis-RA improved (> or =30%) lymphocyte and NK cell count in patients with metastatic colorectal cancer (MCRC) that had a clinical benefit from induction chemotherapy. Secondary endpoint was the evaluation of toxicity, progression-free survival (PFS), and overall survival (OS).. Forty patients with MCRC, showing a clinical benefit from chemotherapy, were treated with subcutaneous low-dose IL-2 (1.8 x 10(6) IU) and oral 13-cis-RA (0.5 mg/kg) in order to maintain responses and improve survival through the increase of lymphocyte and NK cells. The biological parameters and the clinical outcome of these patients were compared with those of a control group of patients (80) with a similar disease status, including clinical benefit from chemotherapy.. The most common adverse events were mild cutaneous skin rash and fever. After 4 months and 2 years of biotherapy, a statistically significant improvement was observed in lymphocyte and number of NK cells with respect to baseline values and to controls. After a median follow-up of 36 months, median PFS was 27.8 months, while median OS was 52.9 months.. These data show that maintenance immunotherapy with low-dose IL-2 and oral 13-cis-RA in patients with MCRC showing a clinical benefit from chemotherapy is feasible, has a low toxicity profile, improves lymphocyte and NK cell count. An improvement in the expected PFS and OS was also observed. A randomized trial is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Colorectal Neoplasms; Female; Humans; Interleukin-2; Isotretinoin; Killer Cells, Natural; Lymphocyte Count; Male; Middle Aged; Survival Analysis

Phase II trials of the novel biologic combination isotretinoin (13-cis-retinoic aid) plus recombinant interferon alfa-2a have demonstrated this combination's major activity against advanced squamous cell carcinoma of the skin and cervix. Because this combination has had limited study in other tumors, we initiated a phase II trial of this regimen in patients with metastatic colorectal adenocarcinoma. Sixteen patients with measurable metastatic colon carcinoma who had received no previous chemotherapy were entered on the trial. Patients received recombinant interferon alfa-2a, 6 million units a day subcutaneously, and isotretinoin, 1 mg/kg per day orally in two divided doses. Patients were evaluated for response after 8 weeks of treatment and then continued on therapy until progressive disease was documented. We did not observe complete or partial responses. Two patients experienced minor responses in measurable pulmonary metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5 patients), granulocytopenia (6 patients), neurotoxicity (2 patients), and elevated serum triglyceride levels (2 patients). Although this combination has demonstrated significant activity in squamous cell carcinomas of the skin and cervix, our results suggest that it has little therapeutic activity against advanced colorectal adenocarcinomas.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Recombinant Proteins

The biological agent cetuximab specifically inhibits the epidermal growth factor receptor (EGFR) function. Cetuximab is licensed for treatment of metastatic colorectal carcinoma, as it enhances the efficacy of cytostatic therapy. Acneiform drug eruptions are common side effects. We report two patients with metastatic colorectal carcinoma, who developed a severe acneiform drug eruption on the face and upper part of the body during the treatment with cetuximab. Triple therapy consisting of systemic isotretinoin, topical nadifloxacin and topical corticosteroid produced rapid improvement with moderate cheilitis the only side effect. We conclude that triple therapy is an effective treatment for patients with severe acneiform drug eruptions caused by cetuximab.

Topics: Acneiform Eruptions; Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; Colorectal Neoplasms; Dermatologic Agents; Drug Eruptions; Drug Therapy, Combination; ErbB Receptors; Fluoroquinolones; Humans; Isotretinoin; Male; Middle Aged; Quinolizines; Treatment Outcome

Clinical Trials Referral Resource is designed to serve as a ready reference for oncologists to help identify clinical trials that might be suitable for their patients. We hope it also will enhance accrual to clinical trials by informing practicing oncologists of ongoing protocols. Currently in the United States less than 10% of eligible adult patients are entered on clinical trials. The result is a delay in answering important therapeutic and scientific questions and disseminating therapeutic advances to the general oncology community. It should be emphasized that including a specific trial does not imply that it is more important than another trial. Among the criteria for selection are that the trial is addressing an important question and is not expected to close in the immediate future (less than 1 year), and that initial staging or laboratory tests required for patient eligibility are widely practiced and available. Information on other protocols can be accessed via Physician's Data Query (PDQ). We emphasize that this is an attempt to encourage referral of patients to these trials. We are specifically not soliciting additional members for the cooperative groups, nor are we suggesting how practicing oncologists should be treating patients not in a study. This month's installment of Clinical Trials Referral Resource is devoted to cancer chemoprevention trials. For patient entry information contact the person listed in each individual trial.

Topics: Adult; Aspirin; Colorectal Neoplasms; Double-Blind Method; Head and Neck Neoplasms; Humans; Isotretinoin; Lung Neoplasms; Neoplasms; Neoplasms, Second Primary