isotretinoin and Fatigue

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.

Topics: Acetylation; Aged; Aged, 80 and over; Calcitriol; Cheilitis; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Fatigue; Histones; Humans; Isotretinoin; Middle Aged; Myelodysplastic Syndromes; Pneumonia; Protein Processing, Post-Translational; Treatment Outcome; Valproic Acid

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

The purpose of this study was to test interferon alfa (IFNalpha), 13-cis-retinoic acid (13cRA), and cisplatin biochemotherapy in advanced squamous cell carcinoma (SCC) of the skin.. Patients with advanced skin SCC received IFNalpha (5 x 10(6) IU/m(2), subcutaneous injection, three times a week), 13cRA (1 mg/kg, orally, daily), and cisplatin (20 mg/m(2), intravenous injection, weekly) in a phase II trial. The growth inhibition, cell-cycle, and apoptosis activity of these agents was evaluated in two skin SCC cell lines (SRB1-m7 and SRB12-p9).. Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P =.007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFNalpha in two skin SCC lines.. The rising incidence, morbidity, and mortality of advanced skin SCC are a major challenge for clinical oncologists. Combined 13cRA, IFNalpha, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, non-cross-resistant biologic effects in vitro, which may account for the combination's clinical activity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Squamous Cell; Cell Cycle; Cisplatin; Fatigue; Female; Fever; Humans; Injections, Intravenous; Injections, Subcutaneous; Interferon-alpha; Isotretinoin; Male; Middle Aged; Neutropenia; Skin Neoplasms; Survival Analysis; Treatment Outcome; Tumor Cells, Cultured

The aim of this study was to determine the response rates and toxicity of two regimens containing granulocyte-macrophage-colony stimulating factor (GM-CSF) in combination with interleukin-2 (IL-2) in the treatment of patients with metastatic renal cell carcinoma.. Therapy given in the first trial (Trial 1) consisted of irradiation to the primary tumor or metastatic site, followed by GM-CSF 100 microg/day administered subcutaneously (sc) for 2 weeks and IL-2 11x10(6) IU sc 4 days per week for 4 weeks. In the second trial (Trial 2), the therapy consisted of GM-CSF 125 microg/day sc for 2 weeks, followed by IL-2 11x10(6) IU sc 4 days per week and interferon-alpha 10x10(6) IU sc 2 days per week for 4 weeks, plus oral 13-cis-retinoic acid 1 mg/kg daily for 4 weeks.. There were no responses among 20 patients in Trial 1, but 3 patients had stable disease. There was 1 partial responder (5%) of 20 evaluable patients in Trial 2 who achieved a complete response with surgical resection. An additional 3 patients maintained stable disease, 2 of whom were rendered disease free by resection of the renal primary and a single metastatic site. The 1-year survival rate was 75% (95% confidence interval [CI], 50-89) in Trial 1 and 48% (95% CI, 20-71) in Trial 2. In Trial 1, Grade 3 toxicities included fever, fatigue, anorexia, nausea/vomiting, hyperbilirubinemia, and mental status change. Toxicity was more frequent in Trial 2 and included Grade 3 fever, fatigue, anorexia, mucositis, and dermatitis. One on-study death may have been therapy-related.. GM-CSF does not enhance the low response rate of IL-2-based immunotherapy for patients with metastatic renal cell carcinoma. New active agents are needed to treat patients with this disease.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antineoplastic Agents; Carcinoma, Renal Cell; Confidence Intervals; Fatigue; Female; Fever; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Injections, Subcutaneous; Interferon-alpha; Interleukin-2; Isotretinoin; Kidney Neoplasms; Male; Middle Aged; Radiotherapy, Adjuvant; Remission Induction; Survival Rate

Recent in vitro and in vivo studies hypothesize a synergistic effect of 13-cis-Retinoic Acid (13cRA) and recombinant alpha-IFN 2a (alpha-IFN) in the treatment of squamous cell carcinoma (SqCC).. 35 patients with SqCC in several sites were treated with 13cRA (0.6-1 mg/kg/day) combined with alpha-IFN (6 x 10(6) I.U./day), continuously for 3 months.. We observed an objective response in 41% of cases (13/32 evaluable patients) with 5 complete and 8 partial responses. Toxicity was mild and always rapidly reversible, with no haematological side effects.. These preliminary data confirm the feasibility and effectiveness of the combination of 13cRA and alpha-IFN in the therapy of SqCC, also in pre-treated patients, with acceptable toxicity and good compliance.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Carcinoma, Squamous Cell; Combined Modality Therapy; Fatigue; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Middle Aged; Recombinant Proteins; Remission Induction

Isotretinoin has revolutionized the management of acne vulgaris. However, concerns continue regarding the adverse effect profile of isotretinoin. This study aims to review the adverse effects experienced by patients started on isotretinoin by a single dermatologist.. Retrospective chart review of 1743 patients started on isotretinoin for various dermatological conditions over a 6-year period. Details of the dose of isotretinoin used, concomitant medications, adverse effects and outcome were recorded.. One-fifth (18.5%) of patients reported no adverse effects during the study period. Cheilitis was the most commonly reported adverse effect, affecting 78% of users, followed by eczema and tiredness, seen in 12% each. However, these were clearly dose-dependent, as the group treated with doses of isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7% and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those treated with more than 0.75 mg/gm/day. Twenty-four patients (1.4%) stopped isotretinoin because of adverse effects; a further three patients complained of severe adverse effects on at least one occasion, but continued taking the medication. The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2). There were no reported instances of suicidal ideation or attempted suicide.. Other than the two oral contraceptive failures, there were no serious adverse events recorded during this review period. Isotretinoin is a very effective medication with a low adverse-effect profile when used at lower doses.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; Aged, 80 and over; Cheilitis; Child; Dermatologic Agents; Dose-Response Relationship, Drug; Eczema; Fatigue; Female; Humans; Isotretinoin; Male; Middle Aged; Mood Disorders; Pregnancy, Unplanned; Retrospective Studies; Young Adult

Topics: Acne Vulgaris; Acute Disease; Adult; Fatigue; Female; Humans; Isotretinoin; Keratolytic Agents; Male; Muscle Weakness; Muscular Diseases; Pain