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Title: | International rare cancers initiative multicenter randomized phase II trial of cisplatin and fluorouracil versus carboplatin and paclitaxel in advanced anal cancer: InterAAct. | Authors: | Bridgewater J.;Cunningham D.;Arnold D.;Glynne-Jones R.;Rao S.;Sclafani F.;Eng C.;Adams R.A.;Guren M.G.;Sebag-Montefiore D.;Benson A.;Bryant A.;Peckitt C.;Segelov E. ;Bhide S.;Roy A.;Seymour M.T.;Welch J.;Saunders M.P.;Muirhead R.;O'Dwyer P. | Monash Health Department(s): | Oncology | Institution: | (Rao, Sclafani, Bryant, Peckitt, Cunningham) Royal Marsden Hospital, London, United Kingdom (Eng) MD Anderson Cancer Center, Houston, TX, United States (Adams) Velindre Cancer Centre, Cardiff, United Kingdom (Guren) Oslo University Hospital, Oslo, Norway (Sebag-Montefiore, Seymour) Leeds Cancer Centre, Leeds, United Kingdom (Benson) Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, United States (Segelov) Monash Health and Monash University, Melbourne, VIC, Australia (Roy) Flinders University, Flinders Medical Centre, Adelaide, SA, Australia (Welch) National Cancer Institute, Bethesda, MD, United States (Saunders) Christie Cancer Centre, Manchester, United Kingdom (Muirhead) University of Oxford, Oxford, United Kingdom (O'Dwyer) Eastern Cooperative Oncology Group, American College of Radiology Imaging Network, Philadelphia, PA, United States (Bridgewater) University College Hospital, London, United Kingdom (Bhide) Institute of Cancer Research, London, United Kingdom (Glynne-Jones) Hamburg University Medical Centre, Hamburg, Germany | Issue Date: | 9-Nov-2020 | Copyright year: | 2020 | Publisher: | American Society of Clinical Oncology (E-mail: jcoservice@asco.org) | Place of publication: | United States | Publication information: | Journal of Clinical Oncology. 38 (22) (pp 2510-2518), 2020. Date of Publication: 12 Jun 2020. | Journal: | Journal of Clinical Oncology | Abstract: | PURPOSE To compare cisplatin plus fluorouracil (FU) versus carboplatin plus paclitaxel in chemotherapy-naive advanced anal cancer to establish the optimal regimen. PATIENTS AND METHODS Patients who had not received systemic therapy for advanced anal cancer were randomly assigned 1:1 to intravenous cisplatin 60 mg/m2 (day 1) plus FU 1,000 mg/m2 (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m2 (days 1, 8, and 15) every 28 days for 24 weeks, until disease progression, intolerable toxicity, or withdrawal of consent. Primary end point was objective response rate (ORR). Primary and secondary end points were assessed in a hierarchic model to compare the regimens and pick the winner. RESULTS We conducted an international multicenter randomized phase II study in 60 centers between December 2013 and November 2017. Median follow-up was 28.6 months. A total of 91 patients were randomly assigned: 46 to cisplatin plus FU and 45 to carboplatin plus paclitaxel. ORR was 57% (95% CI, 39.4% to 73.7%) for cisplatin plus FU versus 59% (95% CI, 42.1% to 74.4%) for carboplatin plus paclitaxel. More serious adverse events were noted in the cisplatin plus FU arm (62%) compared with the carboplatin plus paclitaxel arm (36%; P 5 .016). Median progression-free survival was 5.7 months (95% CI, 3.3 to 9.0 months) for cisplatin plus FU compared with 8.1 months (95% CI, 6.6 to 8.8 months) for carboplatin plus paclitaxel. Median overall survival was 12.3 months for cisplatin plus FU (95% CI, 9.2 to 17.7 months) compared with 20 months (95% CI, 12.7 months to not reached) for carboplatin plus paclitaxel (hazard ratio, 2.00; 95% CI, 1.15 to 3.47; P 5 .014). CONCLUSION This is the first international randomized trial to our knowledge conducted in chemotherapy-naive advanced anal cancer. Although there was no difference in ORR, the association with clinically relevant reduced toxicity and a trend toward longer survival suggest that carboplatin plus paclitaxel should be considered as a new standard of care.Copyright © 2020 American Society of Clinical Oncology. All rights reserved. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1200/JCO.19.03266 | PubMed URL: | 32530769 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32530769] | ISSN: | 0732-183X | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/28962 | Type: | Article | Subjects: | progression free survival randomized controlled trial thrombocytopenia/si [Side Effect] thromboembolism/si [Side Effect] treatment response vomiting/si [Side Effect] *carboplatin/ae [Adverse Drug Reaction] *carboplatin/ct [Clinical Trial] *carboplatin/cb [Drug Combination] *carboplatin/cm [Drug Comparison] *carboplatin/dt [Drug Therapy] *carboplatin/tm [Unexpected Outcome of Drug Treatment] *cisplatin/ae [Adverse Drug Reaction] *cisplatin/ct [Clinical Trial] *cisplatin/cb [Drug Combination] *cisplatin/cm [Drug Comparison] *cisplatin/dt [Drug Therapy] *cisplatin/iv [Intravenous Drug Administration] *cisplatin/tm [Unexpected Outcome of Drug Treatment] *fluorouracil/ae [Adverse Drug Reaction] *fluorouracil/ct [Clinical Trial] *fluorouracil/cb [Drug Combination] *fluorouracil/cm [Drug Comparison] *fluorouracil/dt [Drug Therapy] *fluorouracil/tm [Unexpected Outcome of Drug Treatment] *paclitaxel/ae [Adverse Drug Reaction] *paclitaxel/ct [Clinical Trial] *paclitaxel/cm [Drug Comparison] *paclitaxel/dt [Drug Therapy] *paclitaxel/tm [Unexpected Outcome of Drug Treatment] *paclitaxel/cb [Drug Combination] adult *advanced cancer/dt [Drug Therapy] aged anemia/si [Side Effect] *anus cancer/dt [Drug Therapy] article cancer combination chemotherapy cancer patient cancer survival controlled study diarrhea/si [Side Effect] drug dose reduction fatigue/si [Side Effect] febrile neutropenia/si [Side Effect] female follow up hearing impairment/si [Side Effect] heart arrhythmia/si [Side Effect] human infection/si [Side Effect] major clinical study male mucosa inflammation/si [Side Effect] multicenter study multiple cycle treatment nausea/si [Side Effect] neuropathy/si [Side Effect] neutropenia/si [Side Effect] open study overall response rate overall survival phase 2 clinical trial priority journal diarrhea / side effect drug dose reduction fatigue / side effect febrile neutropenia / side effect female follow up hearing impairment / side effect heart arrhythmia / side effect human infection / side effect major clinical study male mucosa inflammation / side effect multicenter study multiple cycle treatment nausea / side effect neuropathy / side effect neutropenia / side effect open study overall response rate overall survival phase 2 clinical trial priority journal *advanced cancer / *drug therapy randomized controlled trial thrombocytopenia / side effect thromboembolism / side effect treatment response vomiting / side effect adult progression free survival aged anemia / side effect *anus cancer / *drug therapy Article cancer combination chemotherapy cancer patient cancer survival controlled study |
Type of Clinical Study or Trial: | Randomised controlled trial |
Appears in Collections: | Articles |
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