mercaptopurine and Ovarian-Neoplasms

Topics: Chemotherapy, Cancer, Regional Perfusion; Chlorambucil; Choriocarcinoma; Chorionic Gonadotropin; Cyclophosphamide; Dactinomycin; Drug Therapy, Combination; Female; Gonadal Steroid Hormones; Humans; Hysterectomy; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Ovarian Neoplasms; Postoperative Care; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Vinblastine

BRCA1 and BRCA2 genes are critical in homologous recombination DNA repair and have been implicated in familial breast and ovarian cancer tumorigenesis. Tumour cells with these mutations demonstrate increased sensitivity to cisplatin and poly (ADP-ribose) polymerase (PARP) inhibitors. 6MP was identified in a screen for novel drugs and found to selectively kill BRCA-defective cells in a xenograft model as effectively as the PARP inhibitor AGO14699, even after these cells had acquired resistance to a PARP inhibitor or cisplatin. Exploiting the genetic basis of these tumours enables us to develop a more tailored approach to therapy for patients with BRCA mutated cancers.. This multi-centre phase II single arm trial was designed to investigate the activity and safety of 6-mercaptopurine (6MP) 55 mg/m² per day, and methotrexate 15 mg/m² per week in patients with advanced breast or ovarian cancer, ECOG PS 0-2, progressing after ≥ one prior regimen and known to bear a BRCA1/2 germ line mutation. Accrual was planned in two stages, with treatment continuing until progression or unacceptable toxicity; in the first, if less than 3/30 evaluable patients respond at 8 weeks after commencing treatment, the trial will be stopped for futility; if not, then accrual would proceed to a second stage, in which if more than 9/65 evaluable patients are found to respond at 8 weeks, the treatment will be regarded as potentially effective and a phase III trial considered subject to satisfactory safety and tolerability. The primary outcome is objective response at 8 weeks, defined by RECISTS v1.1 as complete response, partial response or stable disease. Secondary outcomes include safety, progression- free and overall survival, and quality of life.. This study aims to investigate whether 6MP might be an effective treatment for BRCA deficient tumours even after the development of resistance to PARP inhibitors or platinum drugs. The study has surpassed the first stage analysis criteria of more than 3 out of 30 evaluable patients responding at 8 weeks, and is currently in the second stage of recruitment.. NCT01432145 http://www.ClinicalTrials.gov.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Protocols; Female; Genes, BRCA1; Genes, BRCA2; Germ-Line Mutation; Humans; Mercaptopurine; Methotrexate; Ovarian Neoplasms

We propose a Bayesian approach for estimating the hazard functions under the constraint of a monotone hazard ratio. We construct a model for the monotone hazard ratio utilizing the Cox's proportional hazards model with a monotone time-dependent coefficient. To reduce computational complexity, we use a signed gamma process prior for the time-dependent coefficient and the Bayesian bootstrap prior for the baseline hazard function. We develop an efficient MCMC algorithm and illustrate the proposed method on simulated and real data sets.

Topics: Algorithms; Bayes Theorem; Computer Simulation; Female; Humans; Leukemia; Markov Chains; Mercaptopurine; Monte Carlo Method; Ovarian Neoplasms; Proportional Hazards Models; Stochastic Processes

Lymphoma can rarely present as an ovarian tumor in children. We describe the unusual case of a 14-year-old adolescent with a locally disseminated ovarian anaplastic large-cell lymphoma, treated with surgery followed by chemotherapy, and who remains disease free at 2 years after diagnosis.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Female; Humans; Long QT Syndrome; Lymph Node Excision; Lymphoma, Large-Cell, Anaplastic; Mercaptopurine; Methotrexate; Omentum; Ovarian Neoplasms; Ovariectomy; Postoperative Complications; Prednisone; Remission Induction; Sepsis; Tumor Lysis Syndrome; Vincristine

Ovarian carcinomas are highly sensitive to chemotherapy. The alkylating agents were most extensively investigated. With these drugs remissions can be obtained in about 50% of the patients. Some early results seem to show a higher response rate and a longer duration of remission after combination chemotherapy. In ovarian carcinoma it has to be the aim of the chemotherapy to obtain a complete remission. The indications for chemotherapy are not yet well defined. Treatment is definitely indicated in stage IV (FIGO) or in recurrent disease after radiotherapy. This treatment has to be given as a long-term therapy over a long period of time. In stage III and II b disease a combined treatment plan has to be developed by the radio- and chemotherapist. At the present time no data are available which prove or disprove the value of an adjuvant chemotherapy in the early stages of ovarian carcinoma. Remembering the somewhat promising results of adjuvant chemotherapy in breast cancer, it is conceivable that prophylactic chemotherapy will prove to be indicated in early stages of ovarian carcinoma.

Topics: Altretamine; Antineoplastic Agents; Chlorambucil; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Hydroxyprogesterones; Mechlorethamine; Melphalan; Mercaptopurine; Methotrexate; Mitomycins; Nitrosourea Compounds; Ovarian Neoplasms; Thiotepa; Vinblastine; Vincristine

Topics: Antineoplastic Agents; Drug Evaluation; Female; Humans; Mercaptopurine; Middle Aged; Ovarian Neoplasms

Topics: Animals; Antineoplastic Agents; Cell Line; Chromosome Aberrations; Drug Resistance; Female; Melphalan; Mercaptopurine; Mitosis; Ovarian Neoplasms; Rats; Thiotepa

Topics: Animals; Chromosomes; Cytogenetics; Female; Mercaptopurine; Neoplasms, Experimental; Ovarian Neoplasms; Rats; Thiotepa

Topics: Antineoplastic Agents; Busulfan; Carcinoma, Squamous Cell; Child; Chlorambucil; Choriocarcinoma; Dactinomycin; Female; Fluorouracil; Gonadal Steroid Hormones; Hodgkin Disease; Humans; Hydrazines; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mesenchymoma; Methotrexate; Multiple Myeloma; Nitrogen Mustard Compounds; Ovarian Neoplasms; Pregnancy; Prostatic Neoplasms; Steroids; Testicular Neoplasms; Urethane; Vinblastine; Vincristine; Wilms Tumor