isotretinoin and Diarrhea

Combining chemotherapy and immunotherapeutic agents such as interleukin-2 and interferon alpha-2b might improve treatment results in metastatic melanoma (MM) patients compared with chemotherapy alone. This prospective study evaluated the potential efficacy of a biochemotherapy regimen followed by maintenance biotherapy for the treatment of MM. Twenty-two patients with stage IV melanoma were treated for 5 consecutive days with cisplatin at 20 mg/m, vinblastine at 1.6 mg/m, and dacarbazine at 160 mg/m. Pegylated interferon alpha-2b at a dose of 50 microg every week, subcutaneous interleukin-2, 1.8 MIU, and oral 13-cis-retinoic acid (13-cis-RA) at 0.5 mg/kg were given 5 days/week for 3 weeks each month during the period of chemotherapy administration. Maintenance biotherapy was continued in patients who had a complete or partial response or disease stability (clinical benefit) after six courses of biochemotherapy. The primary endpoint was response; secondary endpoints were the evaluation of the immunologic parameters, toxicity, progression-free survival, and overall survival. Twelve patients (54.5%) achieved a response, and seven (31.8%) maintained stable disease for at least 6 months with maintenance biotherapy. The median progression-free survival and overall survival were 23.3 and 45.7 months, respectively. The most important toxicities from chemotherapy were grades 3 and 4 neutropenia and thrombocytopenia in 41 and 18% of patients, respectively, whereas grade 2 autoimmune reactions were observed in 21% of patients after maintenance biotherapy. A prolonged enhancement of immunologic function was observed in the 19 patients treated with maintenance therapy. A regimen of six cycles of biochemotherapy followed by maintenance immunotherapy is well tolerated, and shows significant activity in patients with MM.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Dacarbazine; Dexamethasone; Diarrhea; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Therapy; Female; Humans; Immunotherapy; Interferon alpha-2; Interferon-alpha; Interleukin-2; Isotretinoin; Magnesium Sulfate; Male; Melanoma; Middle Aged; Neutropenia; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Treatment Outcome; Vinblastine

(1) Isotretinoin, a vitamin A derivative, is marketed as an oral treatment for refractory severe acne. It is known to carry a risk of severe birth defects. The skin tends to become dry and fragile during isotretinoin treatment; (2) Some adverse effects of isotretinoin are caused by damage to the intestinal mucosae. These effects include bloody and mucousy diarrhoea, colitis, ileitis (sometimes severe and necessitating surgery), and aggravation of inflammatory bowel disease such as Crohn's disease; (3) Isotretinoin can affect all mucous membranes, causing multiple disorders of varying severity, affecting: the eyes (conjunctivitis); ear, nose and throat (epistaxis); respiratory tract; gastrointestinal tract (colitis); and urinary tract; (4) Patients must be informed of the risk of mucosal damage and especially of intestinal disorders associated with isotretinoin therapy. Isotretinoin should be borne in mind as a possible cause when a young patient presents with gastrointestinal disorders, and its withdrawal should be envisaged. Isotretinoin is an additional risk factor in patients with a personal or familial history of inflammatory bowel disease.

Topics: Acne Vulgaris; Adolescent; Adult; Colitis; Crohn Disease; Diarrhea; France; Humans; Inflammatory Bowel Diseases; Intestinal Diseases; Intestines; Isotretinoin; Mucous Membrane; United States; Young Adult

A case of collagenous colitis in a young man treated by isotretinoïn raises the hypothesis of an isotretinoïn inducedcess on the oossible account of atoov and auto-immunity in the family.

Topics: Acne Vulgaris; Adult; Antibodies, Antinuclear; Autoimmunity; Colitis, Collagenous; Diagnosis, Differential; Diarrhea; Food Hypersensitivity; Humans; Isotretinoin; Male

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may undergo spontaneous differentiation or regression due to apoptosis after no or minimal therapy. However, the majority of neuroblastomas are diagnosed as metastatic tumours with a poor prognosis in spite of intensive multimodal therapy. Vitamin A and its analogues (retinoic acid, RA) play an important role in normal cel lular differentiation and programmed cell death. RA regulates neuroblastoma growth and differentiation in vitro, and has shown activity against human neuroblastoma in vivo.. Recently, 9-cis RA was shown to induce apoptosis in vitro in neuroblastoma using a 5 days short-term treatment and subsequent washout. In the present study, nude rats with human neuroblastoma SH-SY5Y xenografts were treated with 13-cis RA (4 mg po daily), 9-cis RA (5 mg po daily) or the novel analogue Ro 13-6307 (0.3 mg po daily) using either a continuous or short-term schedule.. ALL three different retinoids decreased neuroblastoma growth significantly in terms of tumour weight after 8-12 days when compared to untreated controls (P < 0.05). Minor signs of toxicity in 13-cis RA treated rats were observed. However, severe toxicity with significant weight loss was seen in all rats treated with 9-cis RA and Ro 13-6307. Toxicity was more pronounced with the continuous regimen.. We conclude that different retinoids reduce neuroblastoma tumour growth in vivo. Drug scheduling and dosage may affect both therapeutic efficacy and toxic side effects. Further in vivo studies are warranted, including pharmacokinetic and molecular analyses, before clinical trials with promising retinoids like 9-cis RA and Ro 13-6307 can be started in children with neuroblastoma.

Topics: Alitretinoin; Animals; Antineoplastic Agents; Body Weight; Cell Differentiation; Cell Division; Diarrhea; Drug Administration Schedule; Fatty Acids, Unsaturated; Female; Humans; Isotretinoin; Male; Mice; Neoplasm Transplantation; Neuroblastoma; Rats; Rats, Nude; Tretinoin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays