isotretinoin and Anemia

The efficacy of human recombinant erythropoietin (rEPO) in myelodysplastic syndromes (MDS) has generally been best in untransfused patients with 'refractory anaemia' according to the World Health Organization (WHO). We treated 63 MDS patients [excluding refractory anaemia with excess blasts, type 2 (RAEB2)] with a previously tested combination of 13-cis-retinoic acid and dihydroxylated vitamin D3 +/- 6-thioguanine in addition to rEPO. Most patients were categorized as refractory cytopenia with multilineage dysplasia and RAEB1, with intermediate 1 International Prognostic Scoring System (IPSS) score; all had Hb <95 g/l, and 70% required regular erythrocyte transfusions. Treatment was well tolerated, and erythroid response rate according to new International Working Group criteria was 60%: 50% in RAEB1 and 64% in non-RAEB patients (P = 0.383). Response rate was not affected by transfusion requirement (63%; 58% in untransfused), IPSS and WHO Prognostic Scoring System scores, and weekly rEPO dosage (30-50 000 U vs. 80 000 U). Median response duration was 16 months. Median survival reached 14 months for RAEB1 and 55 months for non-RAEB patients, with a significant difference in the latter between responders and non-responders (median 82 months vs. 44 months; P = 0.036). Our combined therapy, independent of rEPO dosage, achieved in patients with unfavourable response predictors, a rate of anaemia improvement comparable to the best obtained in lower risk patients by high-dose rEPO.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Calcitriol; Drug Therapy, Combination; Erythropoietin; Female; Humans; Isotretinoin; Kaplan-Meier Estimate; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Risk; Survival Rate; Treatment Outcome; Vitamins

Combined biological therapy with 13-cis-retinoic acid (13-cRA) and interferon alpha-2a (IFN alpha-2a) was reported to be highly effective in squamous cell carcinoma of the cervix and skin. Squamous cell carcinoma of the penis is rare in the United States, accounting for less than 1/2% of all male malignancies. Because of the association of infection with human papillomavirus with both carcinomas of the cervix and penis and their shared squamous cell histology, we carried out a phase II study of 13-cRA and IFN alpha-2a in carcinoma of the penis.. Eighteen ambulatory patients with surgically unresectable, recurrent, and/or metastatic squamous cell carcinoma of the penis were treated with IFN alpha-2a, 3MU/day administered subcutaneously and 13-cRA, 1 mg/kg orally daily for at least eight weeks, unless intolerable toxicity occurred.. One patient was ineligible; one patient withdrew prior to treatment. Among the 16 eligible, treated patients, there was one complete response. Fourteen patients had progressive disease as their only treatment effect. Two patients were unevaluable for tumor response because they had no follow-up tumor measurements. No unexpected treatment-related toxicities were found on study. The only common form of grade 3 toxicity was hypertriglyceridemia found in eight of the 17 patients (47%). No toxicities above grade 3 were observed.. In contrast to its benefit in squamous cell carcinomas of the cervix and skin, the combination of 13-cRA and IFN alpha-2a has low efficacy in advanced carcinoma of the penis.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease Progression; Fatigue; Fever; Humans; Hypertriglyceridemia; Interferon alpha-2; Interferon-alpha; Isotretinoin; Life Tables; Male; Middle Aged; Penile Neoplasms; Recombinant Proteins; Survival Analysis; Treatment Failure

A pilot study was performed to determine the efficacy of 13-cis-retinoic acid (CRA) and alpha-tocopherol (AT) with increasing doses of recombinant human erythropoietin (rHuEPO) in anemic patients with primary myelodysplastic syndrome (MDS), to determine response rate and to determine the dose requirement and long-term effects of rHuEPO therapy on the transition to acute non-lymphocytic anemia and survival of these patients. Twenty-four consecutive MDS patients were entered into the study. Patients were stratified according to their FAB classification at study entry. Therapy consisted of a 6 month trial of CRA (100 mg m(-2) day(-1) and AT (800 mg day(-1)) with rHuEPO (150 units kg(-1) body weight subcutaneously three times a week). The rHuEPO dose was escalated to daily doses at 2 months, and 300 U kg(-1) body weight given three times a week for another 2 months and continuing therapy after 6 months in responsive patients. Response was measured by elimination of transfusions requirement (partial response, PR) and normal hemoglobin level and complete blood counts (complete response, CR). Observed responses for the 23 evaluable patients were 2 CR and 6 PR (34.8%). Odds ratio analysis showed that patients with anemia alone were 14 times more likely to respond than patients with pancytopenia (p = 0.06). In our study, two patients (8%) transformed to acute leukemia in CRA + AT + rHuEPO-treated patients. Median survival of 34 months with a median follow-up of 17 months (range 3-70 months) was observed. The response rates with the addition of rHuEPO to CRA and AT was similar but occurs earlier at 2 months compared to 6-10 months with CRA and AT alone and did not alter survival. There was no increase in the risk for leukemia in the group treated with rHuEPO. Response to either therapy appeared to be limited to patients in the early stages of MDS.

Topics: Aged; Anemia; Erythropoietin; Female; Humans; Isotretinoin; Male; Middle Aged; Myelodysplastic Syndromes; Pilot Projects; Recombinant Proteins; Treatment Outcome; Vitamin E

Topics: Acne Vulgaris; Adult; Anemia; Dermatologic Agents; Female; Folic Acid Deficiency; Humans; Isotretinoin; Vitamin B 12 Deficiency

Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.

Topics: Anemia; Bone Marrow; Bone Marrow Cells; Cell Division; Clone Cells; Dexamethasone; Humans; Isotretinoin; Karyotyping; Male; Middle Aged; Monocytes; Myelodysplastic Syndromes; Tretinoin

Moderate anemia was present in 25% and low serum iron levels in 75% of patients with severe nodulocystic acne. These findings, combined with an elevated serum ferritin level and normal transferrin saturation, indicate that the low serum iron levels and anemia are secondary to the chronic disease state of cutaneous inflammation rather than an iron-deficiency state. Successful therapy of the severe cystic acne with isotretinoin (13-cis-retinoic acid) resulted in return of serum iron and hemoglobin values to normal levels and a decrease in serum ferritin level.

Topics: Acne Vulgaris; Adolescent; Adult; Anemia; Ferritins; Hemoglobins; Humans; Iron; Isotretinoin; Transferrin; Tretinoin