ABCB1 and SLCO1B1 gene polymorphisms predict methotrexate-resistant for low-risk gestational trophoblastic neoplasia

2021 ◽  
Vol 18 (2) ◽  
pp. 107-114
Author(s):  
Manasawee Srisuttayasathien ◽  
Nutthada Areepium ◽  
Ruangsak Lertkhachonsuk

Aim: The aim of this study was to explore the effects of ABCB1 and SLCO1B1 gene polymorphisms and the methotrexate (MTX) treatment response in patients with low-risk gestational trophoblastic neoplasia (GTN). Materials & methods: Low-risk GTN patients who received MTX as a first-line single agent were enrolled. DNA was extracted from peripheral blood samples from 18 patients and assessed for ABCB1 C3435T and SLCO1B1 T521C. Results: ABCB1 C3435T and SLCO1B1 T521C polymorphisms were not associated with the MTX response or toxicity in Thai patients Conclusion: The selected ABCB1 and SLCO1B1 polymorphism do not predict the risk of MTX resistance in low-risk GTN.

2016 ◽  
Vol 26 (5) ◽  
pp. 971-976 ◽  
Author(s):  
Fariba Yarandi ◽  
Azamsadat Mousavi ◽  
Fereshteh Abbaslu ◽  
Soheila Aminimoghaddam ◽  
Sepideh Nekuie ◽  
...  

ObjectivesMethotrexate (MTX) and Actinomycin-D (Act-D) are effective drugs used in the treatment of low-risk gestational trophoblastic neoplasia (LRGTNs). The aim of the present study was to compare intravenous (IV) MTX and IV Act-D in the treatment of LRGTNs.Materials and MethodsSixty-two patients with LRGTN were enrolled in a prospective randomized clinical trial between 2010 and 2013 in Moheb e Yas Hospital, Tehran University of Medical Sciences. Primary treatment regimens were IV MTX, 0.4 mg/kg daily for 5 days every 14 days (25 mg maximum daily dose), and IV Act-D, 1.25 mg/m2 (2 mg maximum dose) every 14 days.ResultsThirty-two and 30 patients were enrolled to MTX and Act-D groups, respectively. Complete remission after receiving first-line chemotherapy was achieved in 79% of all cases, 80% in the Act-D group and 78.1% in the MTX group.Twenty percent of the Act-D patients and 21.9% of the MTX patients showed resistance to the first-line chemotherapy, of which 16.7% and 15.6% responded completely to the second-line monotherapy, respectively. Multiple drug therapy was needed in 3.3% of the Act-D group and 6.3% of the MTX group.We did not find any correlation between treatment response and beta–human chorionic gonadotropin level, uterine mass size, lung metastasis, antecedent pregnancy, and duration from diagnosis to treatment. Adverse effects were not statistically different between the 2 groups.ConclusionsSingle-agent chemotherapy in the treatment of LRGTNs resulted in an overall complete remission rate of 79%, 80% in the Act-D group and 78.1% in MTX group, with no statistically significant difference. Whereas this study represents an important step in comparing single-agent treatments, comparison of other regimens will be required to determine the optimal single-agent therapy.


Author(s):  
Rakesh M. P. ◽  
Kalaichelvi K. ◽  
Govind Gangadharan ◽  
Vishnu Sreedath

Background: Gestational trophoblastic disease (GTD) comprises a spectrum of diseases ranging from molar pregnancy to malignant gestational trophoblastic neoplasia (GTN). GTN are highly chemo-sensitive tumours which are treated as per FIGO risk stratification. The rarity of the disease limits the evidence regarding the disease to case series and reports. The objective of this study was to study incidence, baseline characteristics of patients and clinical outcome of GTN patients treated at this centre.Methods: This is a retrospective descriptive study based on medical records of patients of GTD who were registered in department of medical oncology, from January 2015 to December 2018 (4 years). GTN was diagnosed based on serum beta HCG values. Their baseline characteristics, risk score, serum β HCG levels, and treatment regimens were investigated. The incidence of GTD and response to treatment were analysed.Results: Out of 211 GTD patients, 56 developed GTN. The incidence was 3.4 per 10000 deliveries. Low risk cases (n=38) were treated with methotrexate and actinomycin in first line while high risk cases received EMACO and EP followed by EMACO as the first line. A cure rate of 100% for low risk cases and 94.4% (n=17) for high risk cases were recorded. Resistance to MTX was 32.3% while EMACO was resistant in 46.6% as first line. Neutropenia and alopecia were the most common treatment related adverse events. Predictors of resistance to single agent in low risk GTN include higher pre-treatment βHCG values and higher risk scores.Conclusions: GTN exemplifies a rare, highly aggressive but curable malignancy. Serum βHCG is the most reliable diagnostic as well as prognostic marker in management of GTD. EMACO is the preferred regimen for high risk GTN. FIGO staging and risk stratification help in individualizing the treatment to ensure maximum response to therapy thus making GTN a curable malignancy.


Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 940-944 ◽  
Author(s):  
Caroline M. P. W. Mandigers ◽  
Jules P. P. Meijerink ◽  
Ewald J. B. M. Mensink ◽  
Evelyn L. R. T. M. Tönnissen ◽  
Konnie M. Hebeda ◽  
...  

In follicular lymphoma, the t(14;18) status of the peripheral blood and bone marrow analyzed by polymerase chain reaction (PCR) is assumed to correlate with disease activity in patients with relapsed disease. The clinical significance of quantitating circulating lymphoma cells by real-time PCR is reported in patients on first-line treatment. Thirty-four consecutive patients with previously untreated follicular lymphoma and detectable t(14;18)-positive cells in pretreatment peripheral blood samples were monitored. All patients were treated with standard chemotherapy in combination with interferon alfa-2b. Before and after induction therapy, blood samples were taken for quantitative analysis of t(14;18). At presentation, a median of 262 t(14;18)-positive cells per 75 000 normal cells was found (range, 1-75 000). Patients with lower numbers of circulating tumor cells more frequently had bulky disease (P = .02). Seventy-nine percent of the patients responded clinically to treatment. In 22 of 28 patients, including 4 patients in whom treatment had failed clinically, the number of circulating t(14;18)-positive cells decreased to undetectable or low levels after therapy. In the remaining responding patients, circulating tumor cells persisted after therapy. These quantitative data on circulating t(14;18)-positive cells call into question the usefulness of molecular monitoring of the blood in a group of patients with follicular lymphoma uniformly treated with a noncurative first-line regimen. T(14;18)-positive cells decreased in peripheral blood after treatment, irrespective of the clinical response. Therefore, the significance of so-called molecular remission should be reconsidered in follicular lymphoma.


2018 ◽  
Vol 148 (1) ◽  
pp. 161-167 ◽  
Author(s):  
Izildinha Maestá ◽  
Roni Nitecki ◽  
Neil S. Horowitz ◽  
Donald P. Goldstein ◽  
Marjory de Freitas Segalla Moreira ◽  
...  

2016 ◽  
Vol 26 (5) ◽  
pp. 977-983 ◽  
Author(s):  
Mariel S. Nevado-Gammad ◽  
Agnes L. Soriano-Estrella

ObjectivesSingle-agent chemotherapy has been the standard of treatment for nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia (GTN). However, it is estimated that approximately 12% to 32% of patients given single-agent therapy will require a change of chemotherapy regimen because of drug resistance and/or intolerable toxicity. The Section of Trophoblastic Diseases of the Philippine General Hospital started using the combination of etoposide-actinomycin (EA) as salvage chemotherapy in the early 2000s. This study was carried out to describe the local experience with this salvage chemotherapy.Materials and MethodsThis is a retrospective descriptive study aimed to analyze the efficacy and safety of the EA regimen as salvage treatment for the management of nonmetastatic and low-risk metastatic GTN. Records of the Section of Trophoblastic Diseases of the Philippine General Hospital from January 1, 2002 to June 30, 2014 were reviewed to identify all patients who had a diagnosis of nonmetastatic and metastatic low-risk GTN. Primary remission rate and toxicity profile of all patients who received the EA regimen as salvage treatment were determined.ResultsDuring the study period, a total of 67 cycles of the EA regimen were administered to 15 patients as salvage chemotherapy. Patients received a median of 4 cycles of EA, attaining normal serum beta human chorionic gonadotropin after 2 to 3 cycles. Thirteen of the 15 patients achieved complete remission with the EA regimen, giving a remission rate of 87%. The major toxicity that the patients experienced was myelosuppression. Grade 1/2 anemia was addressed by blood transfusion. Grade 3 neutropenia/myelosuppression was addressed by the administration of granulocyte colony-stimulating factor. Alopecia was seen in all of the patients. One patient experienced dermatitis with accompanying myelosuppression.ConclusionThe EA regimen was efficacious and well tolerated for the treatment of refractory nonmetastatic and low- risk metastatic GTN.


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