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JAMA Oncology Jan 2020Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of...
Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.
IMPORTANCE
Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients.
OBJECTIVE
To evaluate clinical outcomes when HAI chemotherapy is combined with systemic chemotherapy in patients with unresectable IHC.
DESIGN, SETTING, AND PARTICIPANTS
A single-institution, phase 2 clinical trial including 38 patients was conducted with HAI floxuridine plus systemic gemcitabine and oxaliplatin in patients with unresectable IHC at Memorial Sloan Kettering Cancer Center between May 20, 2013, and June 27, 2019. A confirmatory phase 1/2 study using the same therapy was conducted during the same time period at Washington University in St Louis. Patients with histologically confirmed, unresectable IHC were eligible. Resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted. Patients with distant metastatic disease were excluded.
INTERVENTIONS
Hepatic arterial infusion of floxuridine and systemic administration of gemcitabine and oxaliplatin.
MAIN OUTCOMES AND MEASURES
The primary outcome was progression-free survival (PFS) of 80% at 6 months.
RESULTS
For the phase 2 clinical trial at Memorial Sloan Kettering Cancer Center, 42 patients with unresectable IHC were included and, of these, 38 patients were treated (13 [34%] men; median [range] age at diagnosis, 64 [39-81] years). The median follow-up was 30.5 months. Twenty-two patients (58%) achieved a partial radiographic response, and 32 patients (84%) achieved disease control at 6 months. Four patients had sufficient response to undergo resection, and 1 patient had a complete pathologic response. The median PFS was 11.8 months (1-sided 90% CI, 11.1) with a 6-month PFS rate of 84.1% (90% CI, 74.8%-infinity), thereby meeting the primary end point (6-month PFS rate, 80%). The median OS was 25.0 months (95% CI, 20.6-not reached), and the 1-year OS rate was 89.5% (95% CI, 80.2%-99.8%). Patients with resectable regional lymph nodes (18 [47%]) showed no difference in OS compared with patients with node-negative disease (24-month OS: lymph node negative: 60%; 95% CI, 40%-91% vs lymph node positive: 50%; 95% CI, 30%-83%; P = .66). Four patients (11%) had grade 4 toxic effects requiring removal from the study (1 portal hypertension, 2 gastroduodenal artery aneurysms, 1 infection in the pump pocket). Subgroup analysis showed significant improvement in survival in patients with IDH1/2 mutated tumors (2-year OS, 90%; 95% CI, 73%-99%) vs wild-type (2-year OS, 33%; 95% CI, 18%-63%) (P = .01). In the Washington University in St Louis confirmatory cohort, 9 patients (90%) achieved disease control at 6 months; the most common grade 3 toxic effect was elevated results of liver function tests, and median PFS was 12.8 months (1-sided 90% CI, 6.4).
CONCLUSIONS AND RELEVANCE
Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable IHC; further evaluation is warranted.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Colorectal Neoplasms; Deoxycytidine; Female; Floxuridine; Humans; Liver Neoplasms; Male; Middle Aged; Oxaliplatin; Treatment Outcome; Gemcitabine
PubMed: 31670750
DOI: 10.1001/jamaoncol.2019.3718 -
JAMA Surgery Jul 2022Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation.
IMPORTANCE
Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation.
OBJECTIVE
To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021.
MAIN OUTCOMES AND MEASURES
Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test.
RESULTS
A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% [94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07).
CONCLUSIONS AND RELEVANCE
This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cohort Studies; Female; Floxuridine; Humans; Infusion Pumps; Liver Neoplasms; Male; Middle Aged; Retrospective Studies
PubMed: 35544131
DOI: 10.1001/jamasurg.2022.1298 -
Oncogene Jun 2018Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor... (Review)
Review
Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor. Fortunately, the rapid sophistication of genetically engineered mouse models of cancer has begun to shed light on these context-dependent tumor suppressor activities. By using techniques that not only toggle "off" tumor suppressor genes in nascent tumors, but also facilitate the timely restoration of gene function "back-on again" in disease specific contexts, precise mechanisms of tumor suppression can be revealed in an unbiased manner. This review discusses the development and implementation of genetic systems designed to toggle tumor suppressor genes off and back-on again and their potential to uncover the tumor suppressor's tale.
Topics: Alleles; Animals; CRISPR-Cas Systems; Floxuridine; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genetic Engineering; Genetic Vectors; Humans; Mice; Mice, Transgenic; Neoplasms, Experimental; RNA Interference; Recombinases
PubMed: 29540833
DOI: 10.1038/s41388-018-0186-3 -
The Oncologist Dec 20215-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades....
Results with Floxuridine, Actinomycin D, Etoposide, and Vincristine in Gestational Trophoblastic Neoplasias with International Federation of Gynecology and Obstetrics Scores ≥5.
BACKGROUND
5-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades. This study aims to assess the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who had International Federation of Gynecology and Obstetrics (FIGO) scores ≥5.
MATERIALS AND METHODS
A total of 207 patients with GTN who had FIGO scores ≥5 were treated with FAEV as first-line chemotherapy at Peking Union Medical College Hospital between January 2002 and December 2017. Complete remission (CR), resistance, survival, toxicity, and reproductive outcomes were analyzed.
RESULTS
Of the 207 patients treated with FAEV, 9 (4.3%) required a change of chemotherapy owing to toxicity and 1 (0.5%) died of cerebral hernia 5 weeks after commencing treatment. The remaining 197 patients were assessable to determine the response to FAEV; among them, 168 (85.3%) achieved CR with FAEV and 29 (14.7%) developed resistance to FAEV. The 5-year overall survival rate of the entire cohort was 97.4%. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 28.4%, 6.8%, and 6.2% of cycles, respectively. No acute toxicity-related deaths occurred. Five patients developed acute myeloid leukemia 10-50 months after exposure to chemotherapy; another patient developed duodenal cancer 2 years after completing therapy. Sixty-one patients who preserved fertility wanted to become pregnant; 56 of them conceived.
CONCLUSION
The FAEV regimen is an effective primary treatment for patients with GTN who have FIGO scores ≥5 and has predictable and manageable toxicity.
IMPLICATIONS FOR PRACTICE
The most commonly used multiagent chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) is etoposide, methotrexate and actinomycin D/cyclophosphamide and vincristine (EMA/CO) worldwide. However, 5-fluorouracil-based multiagent chemotherapy has been used as a primary treatment for high-risk GTN in China for a few decades. This study evaluated the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who have International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. The study's data demonstrated that FAEV as a primary treatment achieved favorable outcomes for patients with FIGO scores ≥5. Toxicities that result from the FAEV regimen are predictable and manageable. The FAEV regimen may provide another option for the treatment of GTN.
Topics: Dactinomycin; Etoposide; Female; Floxuridine; Gestational Trophoblastic Disease; Humans; Obstetrics; Pregnancy; Vincristine
PubMed: 34396643
DOI: 10.1002/onco.13943 -
The Cochrane Database of Systematic... Oct 2009Liver metastases are often the dominant site of metastatic disease in colorectal cancer. Selective internal radiation therapy (SIRT) involves embolising radiolabeled... (Review)
Review
BACKGROUND
Liver metastases are often the dominant site of metastatic disease in colorectal cancer. Selective internal radiation therapy (SIRT) involves embolising radiolabeled spheres (SIR-Spheres) into the arterial supply of the liver with the aim of improving the control of liver metastases.
OBJECTIVES
To assess the effectiveness and toxicity of SIRT in the treatment of metastatic colorectal cancer liver metastasis when given alone or with systemic or regional hepatic artery chemotherapy.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane library 2008 issue 2, MEDLINE (1966 to October 2008), EMBASE (1980 to October 2008), and Pubmed (October 2008). The proceedings of ASCO (1985 to 2008) and ASCO GI (2004 to 2008) were also searched. The manufacturers of SIR-Spheres were contacted and asked whether they were aware of any other unpublished studies.
SELECTION CRITERIA
Randomised controlled trials comparing SIRT and chemotherapy (systemic and/or regional) with chemotherapy alone, or comparing SIRT alone with best supportive care in patients with metastatic colorectal cancer.
DATA COLLECTION AND ANALYSIS
Two authors (AT/TP) extracted data and assessed the trial quality. The study authors were contacted and individual patient data was obtained. Results were analysed separately for patients with and without extra-hepatic disease.
MAIN RESULTS
A single study of 21 patients compared SIRT and systemic chemotherapy (fluorouracil and leucovorin) with chemotherapy alone. There was a significant improvement in progression free survival and median survival associated with SIRT, both for the total studied population and for those disease limited to the liver. There was an increase in toxicity with the use of SIRT. A second study of 63 eligible patients compared SIRT and regional chemotherapy (floxuridine) with regional chemotherapy alone. There was no significant difference in progression free survival and median survival seen with SIRT, in either the total patient group or in the 22 patients with disease limited to the liver. There was no significant increase in toxicity with the addition of SIRT to regional chemotherapy. There were no randomised studies comparing SIRT with best supportive care in patients with refractory disease, and no randomised studies assessing the effect of SIRT in patients with resectable liver metastases.
AUTHORS' CONCLUSIONS
There is a need for well designed, adequately powered phase III trials assessing the effect of SIRT when used with modern combination chemotherapy regimens. Further studies are also needed for patients with refractory disease with a particular focus on the impact on quality of life.
Topics: Antimetabolites, Antineoplastic; Colorectal Neoplasms; Combined Modality Therapy; Floxuridine; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Microspheres; Radiotherapy; Randomized Controlled Trials as Topic; Yttrium Radioisotopes
PubMed: 19821394
DOI: 10.1002/14651858.CD007045.pub2 -
Annals of Surgical Oncology Sep 2022Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA.
PATIENTS AND METHODS
A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures.
RESULTS
After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0-39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively.
CONCLUSION
HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Floxuridine; Humans; Infusion Pumps; Infusions, Intra-Arterial; Liver Neoplasms; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 35294656
DOI: 10.1245/s10434-022-11439-x -
International Journal of Molecular... Jul 2021In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds...
In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. Using the approach of creating supramolecular amphiphiles, we have developed self-assembling systems based on water-soluble pillar[5]arene and synthetic meroterpenoids containing geraniol, myrtenol, farnesol, and phytol fragments. The resulting systems can be used as universal drug delivery systems. It was shown by turbidimetry that the obtained pillar[5]arene/synthetic meroterpenoid systems do not interact with the model cell membrane at pH = 7.4, but the associates are destroyed at pH = 4.1. In this case, the synthetic meroterpenoid is incorporated into the lipid bilayer of the model membrane. The characteristics of supramolecular self-assembly, association constants and stoichiometry of the most stable pillar[5]arene/synthetic meroterpenoid complexes were established by UV-vis spectroscopy and dynamic light scattering (DLS). It was shown that supramolecular amphiphiles based on pillar[5]arene/synthetic meroterpenoid systems form monodisperse associates in a wide range of concentrations. The inclusion of the antitumor drug 5-fluoro-2'-deoxyuridine (floxuridine) into the structure of the supramolecular associate was demonstrated by DLS, 19F, 2D DOSY NMR spectroscopy.
Topics: Calixarenes; Floxuridine; Membranes, Artificial; Terpenes
PubMed: 34360730
DOI: 10.3390/ijms22157950 -
Biomedicine & Pharmacotherapy =... Jun 2023Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to...
BACKGROUND
Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine.
METHODS
Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed.
RESULTS
265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL [IQR: 0.472-0.747] for cycle 1 day 7, 0.579 ng/mL [IQR: 0.470-0.693] for cycle 1 day 15, 0.646 ng/mL [IQR: 0.463-0.8546] for cycle 2 day 7, and 0.534 ng/mL [IQR: 0.4257-0.7075] for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation. The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %-37.8 %) over a period of 15 days (n = 18).
CONCLUSION
Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time.
Topics: Humans; Floxuridine; Colorectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Liver Neoplasms; Infusion Pumps
PubMed: 37058821
DOI: 10.1016/j.biopha.2023.114625 -
Oncology 2021Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and... (Clinical Trial)
Clinical Trial
BACKGROUND
Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma.
METHODS
Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m2 gemcitabine and predefined doses of cisplatin 25 mg/m2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1-14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported.
RESULTS
The determined MTD for gemcitabine was 800 mg/m2. Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1-49), and median progression-free survival 10.1 months (range 2-40).
CONCLUSIONS
Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Female; Floxuridine; Follow-Up Studies; Hepatic Artery; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Non-Randomized Controlled Trials as Topic; Prognosis; Prospective Studies; Survival Rate; Gemcitabine
PubMed: 33657549
DOI: 10.1159/000512967 -
Efficacies of FAEV and EMA/CO regimens as primary treatment for gestational trophoblastic neoplasia.British Journal of Cancer Aug 2022Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic neoplasia (GTN). However, the floxuridine, actinomycin D, etoposide and vincristine (FAEV) regimen is commonly used to treat these patients in China. We conducted a randomised controlled trial to compare the efficacies and toxicities of FAEV and EMA/CO.
METHODS
Ninety-four patients with GTN were enrolled between May 2015 and April 2019 and randomly assigned to the FAEV or EMA/CO regimen. The rates of complete remission and relapse and the toxicities were compared in August 2021.
RESULTS
Five patients were excluded from the analysis. There were 46 patients in the FAEV group and 43 patients in the EMA/CO group. The complete remission rates following primary treatment were 89.1% and 79.1% (P = 0.193), respectively. The relapse rates were 8.7% and 9.3% (P = 0.604). The apparent incidences of grade 4 myelosuppression were 60.9% and 32.6% (P = 0.008), respectively; however, they became both 32.6% (P = 0.996) after granulocyte colony-stimulating factor support. Other adverse reactions were similar in the two groups. No patient died of disease.
CONCLUSION
FAEV has comparable efficacy and toxicity to EMA/CO as the primary treatment for high-risk GTN, and may thus be another first-line choice of chemotherapy.
CLINICAL TRIAL REGISTRATION
chictr.org.cn: ChiCTR1800017423.
Topics: Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Etoposide; Female; Floxuridine; Gestational Trophoblastic Disease; Humans; Neoplasm Recurrence, Local; Pregnancy; Vincristine
PubMed: 35459802
DOI: 10.1038/s41416-022-01809-3