isotretinoin and Esophageal-Neoplasms

Interferon in combination with 5-fluorouracil has been shown to be active in squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus. 13-cis-retinoic acid (CRA) has chemopreventive activity in SCC of the head and neck, and, in combination with interferon, has antitumor activity in SCC of the skin and cervix.. The activity and toxicity of CRA and interferon-alpha-2a (IFN) in patients with advanced esophageal carcinoma was evaluated in a Phase II single institution trial. Patients had unresectable or metastatic AC or SCC of the esophagus. One prior chemotherapy regimen was allowed. IFN was given by daily subcutaneous injection at a dose of 3 million U and CRA was taken orally at a dose of 1 mg/kg/day in 2 divided doses. Treatment was given in cycles of 4 weeks and continued until documented disease progression.. Of the 19 patients entered, 15 were evaluable for response and toxicity. One patient was evaluable for response only and one patient was evaluable for toxicity only. Evaluable patients were predominantly male (15 patients), and had AC (13 patients). All had AJCC Stage IV disease and 12 were pretreated. Patients completed an average of two cycles of therapy (range, one to six cycles) prior to progression of disease. National Cancer Institute Common Toxicity Criteria Grade 3/4 toxicity was notable for nausea (25%) and fatigue (31%). No major objective responses were recorded. Eleven patients with AC and 3 patients with SCC had rapid progression of disease. One patient with AC was found to have a minor response for 22 weeks and 1 patient with AC had stable disease for 45 weeks.. This regimen had no significant activity in patients with advanced AC of the esophagus. Further evaluation of IFN plus CRA, using this dose and schedule, is not recommended. In comparison with prior trials of this therapy, a surprising amount of severe nausea and fatigue was observed in this trial.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Middle Aged; Recombinant Proteins

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Middle Aged; Recombinant Proteins

The aim of this study was to investigate the possible therapeutic effect of 13-cis-retinoic acid plus interferon alpha-2a in patients with inoperable squamous cancer of the esophagus. Patients with advanced, measurable, histologically confirmed squamous carcinoma of the esophagus with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 who had adequate bone marrow, liver, and renal function were eligible for study. Patients were given cis-retinoic acid 1 mg/kg/day per mouth continuously and interferon alpha-2a 3 Mu/day for 3 days followed by 6 Mu subcutaneously daily thereafter. Seventeen patients were entered on study. Fifteen patients were evaluable for toxicity. The most common toxicities were grade 1 and 2 cheilitis, dry skin and flu-like symptoms which occurred in all patients. Two patients had grade 3 toxicity (1 anorexia and 1 fatigue). No grade 4 toxicity occurred. Fifteen patients were evaluable for response. No objective response was documented. The median survival time was 15 weeks. With no response seen it is unlikely that the combination of treatment as used in this study will be of benefit in patients with advanced squamous cancer of the esophagus.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Middle Aged; Recombinant Proteins

Groups of Charles River Sprague-Dawley male rats were given intragastric intubations of methylbenzylnitrosamine after receiving one of the following diets for 4 weeks: control, zinc-deficient, or zinc-deficient diet plus 4% ethanol in the drinking water. One zinc-deficient group was zinc repleted after the dosing period; the other group, zinc-deficient plus 4% ethanol, received 13-cis-retinoic acid (13-cis-RA) after the dosing period. Zinc deficiency significantly enhanced esophageal tumor incidence; the addition of ethanol further enhanced tumor incidence. Zinc repletion reduced tumor incidence, whereas the addition of 13-cis-RA enhanced tumor incidence.

Topics: Animals; Body Weight; Cocarcinogenesis; Copper; Diet; Dimethylnitrosamine; Esophageal Neoplasms; Ethanol; Isotretinoin; Male; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Tretinoin; Zinc