isotretinoin and Leukopenia

Patients with recurrent small-cell lung cancer (SCLC) have dismal outcomes. The failure of salvage therapy is due to the possible development of resistance mechanisms, such as the upregulation of the anti-apoptosis protein, Bcl-2. We conducted a phase II study to evaluate if modulation of Bcl-2 with 13-cis-retinoic acid (13-CRA) and interferon alpha could improve response rates when combined with paclitaxel in patients with recurrent SCLC.. Patients with recurrent SCLC and measurable disease were treated with interferon alpha at 6 million units/m² subcutaneously and 13-CRA 1 mg/kg orally on days 1 and 2 and paclitaxel 75 mg/m² intravenously on day 2 of each week for 6 weeks of an 8-week treatment cycle. Treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. The primary endpoint was response rate with secondary endpoints of progression-free survival (PFS) and overall survival (OS). Bcl-2 levels were assessed in peripheral blood mononuclear cells (PBMCs).. Thirty-seven patients were enrolled; 34 were included in the intention-to-treat analysis as 3 patients were ineligible for the study. There were 3 partial responses (9 %), and 5 patients had stable disease (15 %) as best response. The median PFS was 2 months, and median OS was 6.2 months. Although mean Bcl-2 protein levels decreased with therapy in PBMCs, there was no association between Bcl-2 levels and response rate or survival.. Despite sound pre-clinical evidence, the addition of 13-CRA and interferon alpha to paclitaxel did not improve outcomes for recurrent SCLC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carcinoma, Small Cell; Chemotherapy-Induced Febrile Neutropenia; Cohort Studies; Early Termination of Clinical Trials; Female; Follow-Up Studies; Humans; Interferon-alpha; Isotretinoin; Leukocytes, Mononuclear; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Proto-Oncogene Proteins c-bcl-2; Severity of Illness Index; Small Cell Lung Carcinoma; Survival Analysis

A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous interferon alfa-2a (IFN) has been reported to yield high response rates in patients with squamous cell carcinomas (SCCAs) of the cervix and skin. Cisplatin and 5-fluorouracil with leucovorin (5-FU/LV) are chemotherapeutic agents commonly used for SCCAs.. To determine the maximum tolerated doses (MTDs) of cisplatin and 5-FU/LV when combined with IFN and cis-RA, and to define a recommended phase II regimen for testing in cervical cancer and other appropriate tumor types.. Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU and LV were administered together as a weekly 24-h infusion. Cis-RA was given orally twice daily. IFN was initially given subcutaneously at a dose of 3 million units (MU) daily.. A total of 31 patients were treated. The IFN dose was reduced to 3 MU three times weekly because of patient intolerance. Cytopenias prevented the administration of weekly 5-FU/LV. Single-agent cisplatin with three times weekly IFN and twice daily cis-RA was tolerable. Four partial responses were observed, in patients with adrenal cancer, bladder cancer, gastric cancer, and adenocarcinoma of unknown primary.. The recommended phase II regimen is cisplatin 100 mg/m2 every 3 weeks, IFN 3 MU three times weekly, and cis-RA 1 mg/kg daily. This appears to be more toxic than single-agent cisplatin, but the preliminary activity observed warrants further testing.

Topics: Administration, Oral; Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Synergism; Female; Fluorouracil; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Isotretinoin; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasms; Recombinant Proteins; Remission Induction

Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care.. We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne.. We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined.. Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3 days for hypertriglyceridemia, 61.9 days for alanine transaminitis, and 50.1 days for hypercholesterolemia.. This was a single-center experience examining variable isotretinoin laboratory monitoring practices.. In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2 months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended.

Topics: Acne Vulgaris; Adolescent; Adult; Alanine Transaminase; Child; Dermatologic Agents; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Isotretinoin; Leukopenia; Liver; Liver Function Tests; Male; Middle Aged; Thrombocytopenia; Young Adult

Topics: Acne Vulgaris; Adult; Agranulocytosis; Humans; Isotretinoin; Leukopenia; Male; Neutropenia; Time Factors; Tretinoin

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosomes, Human, 21-22 and Y; Cytarabine; Daunorubicin; Humans; Isotretinoin; Leukemia, Myeloid; Leukopenia; Liver; Middle Aged; Stomatitis; Thioguanine; Thrombocytopenia; Time Factors; Tretinoin