mercaptopurine and Melanoma

The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients.. MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity.. Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance.. Exposition of thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.

Topics: Azathioprine; Databases, Bibliographic; Humans; Inflammatory Bowel Diseases; Melanoma; Mercaptopurine; Risk; Skin Neoplasms

Crohn's disease (CD) is a chronic inflammatory disease that confers a higher risk of cancer than in the general population. New, large, population-based studies in the past decade show that patients with CD are at higher risk of colorectal, small bowel, melanoma, and cervical cancer. Patients who use thiopurines are at additional risk of development of lymphoma and nonmelanoma skin cancer. Preventive surveillance for cancers of the colorectum, skin, and uterine cervix is advised.

Topics: Colorectal Neoplasms; Crohn Disease; Early Detection of Cancer; Female; Humans; Immunosuppressive Agents; Intestinal Neoplasms; Intestine, Small; Lymphoma; Male; Melanoma; Mercaptopurine; Risk Factors; Skin Neoplasms; Uterine Cervical Neoplasms

Topics: Anatomy; Arthritis; Autoantibodies; Betamethasone; Dexamethasone; Dihydroxyphenylalanine; Epidemiology; Histoplasmosis; Hypersensitivity; Melanoma; Mercaptopurine; Oxyphenbutazone; p-Methoxy-N-methylphenethylamine; Phenothiazines; Physiology; Prednisolone; Prednisone; Sarcoidosis; Toxicology; Toxoplasmosis; Triamcinolone; Uvea; Uveitis; Virus Diseases

Topics: Breast Neoplasms; Clinical Trials as Topic; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Lymphoma; Melanoma; Mercaptopurine; Neoplasms

Topics: Antimetabolites; Colitis, Ulcerative; Female; Humans; Male; Melanoma; Mercaptopurine; Skin Neoplasms

There are limited data on the risk of non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC) among thiopurine-treated patients with ulcerative colitis (UC). Our aim was to investigate the risk while on, by cumulative years, and after stopping thiopurine therapy.. Nationwide data were obtained from the Veterans Affairs (VA) health-care system during 2001-2011. We performed a retrospective cohort study evaluating patients with UC. Cox regression was used to investigate the association between thiopurines use and time to NMSC while adjusting for demographics, ultraviolet radiation exposure, and VA visiting frequency. A matched nested case-control study was conducted to investigate the association between thiopurine use and MSC.. We included 14,527 patients with UC in the analysis, with a median follow-up of 8.1 years. A total of 3,346 (23%) patients used thiopurines for a median duration of 1.6 years. We identified 421 NMSC and 45 MSC cases. The adjusted hazard ratios of developing NMSC while on and after stopping thiopurines were 2.1 (P<0.0001) and 0.7 (P=0.07), respectively, as compared with unexposed patients. The incidence rate of NMSC among those who never used thiopurines was 3.7 compared with 5.8, 7.9, 8.3, 7.8, and 13.6 per 1,000 person-years for the 1st, 2nd, 3th, 4th, and 5th year of thiopurine use, respectively. No statistically significant association was observed between thiopurine use and MSC, odds ratio 0.8 (P=0.6).. In this predominantly white male nationwide cohort, there was a twofold increase in the risk of NMSC while on thiopurines. The incidence rate of NMSC significantly increased with subsequent years of cumulative exposure to thiopurines. Stopping thiopurines reduced the risk of NMSC to pre-exposure levels irrespective of the prior exposure duration.

Topics: Aged; Antimetabolites; Colitis, Ulcerative; Female; Humans; Incidence; Male; Melanoma; Melanoma, Cutaneous Malignant; Mercaptopurine; Middle Aged; Regression Analysis; Retrospective Studies; Risk; Skin Neoplasms; United States; Veterans

Patients with inflammatory bowel disease (IBD) are at risk for certain malignancies. We aimed to determine the risk of melanoma and nonmelanoma skin cancer (NMSC) in patients with IBD and how medications affect these risks.. We performed retrospective cohort and nested case-control studies using administrative data from the LifeLink Health Plan Claims Database from 1997 to 2009. The cohort comprised 108,579 patients with IBD, and each was matched to 4 individuals without IBD. The risk of melanoma and NMSC was evaluated by incidence rate ratio (IRR) and by adjusted Cox proportional hazard ratio (HR) modeling. In nested case-control studies, patients with melanoma or NMSC were matched to 4 patients with IBD without melanoma or NMSC. Conditional logistic regression was used to determine associations between medications and both skin cancers.. In the cohort, IBD was associated with an increased incidence of melanoma (IRR, 1.29; 95% confidence interval [CI], 1.09-1.53). Risk was greatest among individuals with Crohn's disease (IRR, 1.45; 95% CI, 1.13-1.85; adjusted HR, 1.28; 95% CI, 1.00-1.64). The incidence of NMSC also increased among patients with IBD (IRR, 1.46; 95% CI, 1.40-1.53) and was greatest among those with CD (IRR, 1.64; 95% CI, 1.54-1.74). In the nested case-control studies, therapy with biologics increased the risk of melanoma (odds ratio [OR], 1.88; 95% CI, 1.08-3.29). Patients who had been treated with thiopurines had an increased risk of NMSC (OR, 1.85; 95% CI, 1.66-2.05).. Immunosuppression increases the risk of melanoma and NMSC among patients with IBD. The risk of melanoma is increased by use of biologics, and the risk of NMSC is increased by use of thiopurines. Patients with IBD should be counseled and monitored for skin cancer.

Topics: Adult; Antibodies, Monoclonal, Humanized; Case-Control Studies; Cohort Studies; Female; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Logistic Models; Male; Melanoma; Mercaptopurine; Middle Aged; Proportional Hazards Models; Retrospective Studies; Risk; Skin Neoplasms; Tumor Necrosis Factor-alpha; United States

Topics: Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Melanoma; Mercaptopurine; Prospective Studies; Skin Neoplasms

Cell surface gangliosides in human melanoma cell lines were modulated by pretreatment and adaptation to 6-thioguanine and 5-bromo-deoxyuridine. Chemo- and radiation sensitivities were compared in original cell lines and modulated cells by the human tumor colony-forming assay. Modulated cells showed decreased expression of cell surface GM2 and GD2 gangliosides. This reduction was correlated with increased resistance to bleomycin, vincristine, cisplatin and radiation treatment. These results suggest that cell surface GM2 and GD2 ganglioside expression in human melanoma cells is intimately associated with several cellular biological properties, such as drug or radiation sensitivity and cellular differentiation.

Topics: Antineoplastic Agents; Bleomycin; Bromodeoxyuridine; Cell Survival; Chromatography, Thin Layer; Cisplatin; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Resistance; Gangliosides; Humans; Melanoma; Membrane Lipids; Mercaptopurine; Tumor Cells, Cultured; Tumor Stem Cell Assay; Vincristine

Lambdamycin, a chromoglycoside antibiotic like chartreusin was found to be very active against leukemias L 1210 and P 388 and moderate effective against melanoma B 16 and Lewis lung carcinoma of mice. It was nearly without any effect when tested on Walker 256 carcinoma of rats. The effectiveness of lambdamycin was compared with that of cyclophosphamide, 5-fluorouracil and 6-mercaptopurine.

Topics: Animals; Benzopyrans; Carcinoma; Cyclophosphamide; Fluorouracil; Glycosides; Leukemia, Experimental; Melanoma; Mercaptopurine; Mice; Rats

Antitumor activities of a combination chemotherapy with a water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), and a single dose of 6-thioguanine were studied using three obstinate murine tumor systems, i.e., Lewis lung carcinoma, B16 melanoma, and an advanced stage of L1210 leukemia systems. Therapeutically synergistic effect was observed either definitely against 1- or 2-day-old Lewis lung carcinoma and 6-day-old L1210 leukemia or moderately against 1-day-old B16 melanoma. Single intravenous treatment on day 7 after subcutaneous implantation of Lewis lung carcinoma, when the tumors had already metastasized to the lungs, produced a significant regression of tumor and a significant increment in survival time of tumor-bearing mice. In comparative studies, the combination of ACNU and 6-thioguanine showed a greater and a wider spectrum of antitumor activities against these tumors than those obtained by the combination with ACNU and a single dose of 5-fluorouracil, methotrexate, or 6-mercaptopurine. Increment in lethal toxicity for normal and tumor-bearing mice was not observed by the combination of ACNU and 6-thioguanine in contrast to definite increases in this toxicity by the combination of ACNU and 5-fluorouracil. The present experimental results may suggest the clinical utility of the combination chemotherapy with ACNU and 6-thioguanine in the treatment of several solid tumors as well as acute leukemias.

Topics: Animals; Antimetabolites, Antineoplastic; Body Weight; Drug Synergism; Drug Therapy, Combination; Female; Injections, Intraperitoneal; Injections, Intravenous; Leukemia L1210; Lung Neoplasms; Male; Melanoma; Mercaptopurine; Mice; Neoplasms, Experimental; Nimustine; Nitrosourea Compounds; Thioguanine

The authors treated the apigmented melanoma IC-Sofia in hamster with various doses of the following cytostatics: Cyclophosphamide, 6-Mercaptopurine, Vinblastine and Actinomycin D for 7 consecutive days. Determination of the tumor growth inhibition on the 8th day (early test) on the basis of tumor weight in the animals treated and untreated with cytostatics indicates that the tumor used is more sensitive to the effect of Cyclophosphamide and 6-MP and less to Vinblastine and Actinomycin D. Nevertheless sensitivity to cytostatic action is high enough for each of the cytostatic agents, depending upon the applied dose. This gives grounds to the authors to assume that hamster apigmented melanoma IC-Sofia is an adequate model for testing and evaluation of antitumor drugs.

Topics: Animals; Antineoplastic Agents; Cricetinae; Cyclophosphamide; Dactinomycin; Drug Evaluation, Preclinical; Melanoma; Mercaptopurine; Neoplasms, Experimental; Skin Neoplasms; Vinblastine

Topics: Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immune Adherence Reaction; Immunosuppressive Agents; Melanoma; Menstruation; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisolone; Vincristine

Drug screening trials and general treatment of solid tumours in advanced cancer patients have been concerned only with the site of primary origin, regardless of where metastases might have seeded. Since the environment for tumour growth can differ appreciably at various anatomical sites, an investigation was undertaken to determine the effect of metastatic site on response to chemotherapy. Data from 1961 to 1965 of the screening trials of the Eastern Clinical Drug Evaluation Program were utilized. Response and location data extensive enough for analysis represented 6 sites of primary origin and 6 metastatic site groups, totalling 1687 lesions. Analysis of percentage reduction in tumour size after chemotherapy regimens of up to 60 days revealed a significant amount of variation associated with metastatic sites and a non-significant amount associated with sites of primary origin. Advanced primary tumours showed marked variation in responsiveness and some showed a difference in response to different drug groups. Generally, metastases responded better than the advanced primaries from which they were derived, except for those from breast tumours.

Topics: Antineoplastic Agents; Breast Neoplasms; Chlorambucil; Female; Fluorouracil; Genital Neoplasms, Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Melanoma; Mercaptopurine; Mitomycins; Neoplasm Metastasis; Neoplasms

Topics: Antigen-Antibody Reactions; Biomedical Research; Blood Group Antigens; Breast Neoplasms; Colonic Neoplasms; Escherichia coli; Francisella tularensis; gamma-Globulins; Humans; Melanoma; Mercaptopurine; Neoplasms; Pharmacology; Placebos; Skin Tests; Skin Transplantation; Transplantation Immunology

Topics: Antineoplastic Agents; Bone Neoplasms; Dactinomycin; Female; Floxuridine; Fluorouracil; Genital Neoplasms, Female; Humans; In Vitro Techniques; Intestinal Neoplasms; Leukemia; Mechlorethamine; Melanoma; Mercaptopurine; Methotrexate; Neoplasms; Pharyngeal Neoplasms; Respiratory Tract Neoplasms; Stomach Neoplasms; Thiotepa