Daniel H Ahn1, Kavya Krishna2, Marlo Blazer3, Joshua Reardon3, Lai Wei4, Christina Wu5, Kristen K Ciombor2, Anne M Noonan2, Sameh Mikhail2, Tanios Bekaii-Saab6. 1. Department of Internal Medicine, Division of Hematology/Medical Oncology, Mayo Clinic, Phoenix, AZ, USA. 2. Department of Medical Oncology, Ohio State University Wexner Medical Center, Richard Solove Research Institute and James Cancer Hospital, Columbus, OH, USA. 3. Department of Pharmacy, Ohio State University Wexner Medical Center, Richard Solove Research Institute and James Cancer Hospital, Columbus, OH, USA. 4. Center for Biostatistics, Ohio State University, Columbus, OH, USA. 5. Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Atlanta, GA, USA. 6. Department of Internal Medicine, Division of Hematology/Medical Oncology, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA.
Abstract
BACKGROUND: Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is associated with significant toxicities, leading to a high rate of drug discontinuation. We implemented a modified regimen of gemcitabine and nab-paclitaxel (mGNabP) in an attempt to minimize toxicities while maintaining efficacy. METHODS: A total of 79 evaluable patients with metastatic pancreatic adenocarcinoma (mPC) treated with a modified regimen of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 15 of every 28-day cycle were identified from our prospective database. A total of 57 patients received this regimen as first-line treatment and were evaluated for toxicities, progression-free survival (PFS), and overall survival (OS). Overall, 22 patients with advanced or metastatic PC treated with the modified regimen outside the first-line setting were only evaluated for toxicities. RESULTS: The median OS and PFS were 10 months [95% confidence interval (CI) 5.9-13 months] and 5.4 months (95% CI 4.1-7.4 months) for patients that received the modified regimen as first-line therapy. Neurotoxicity occurred in 27% with only 1.6% of patients experiencing grade ⩾3 toxicity. The incidence of grade ⩾3 neutropenia was 19%, resulting in growth factor support in 12% of patients. This rate was similar in patients who received the modified regimen for first-line treatment of mPC versus the overall group. CONCLUSIONS: A modified regimen of biweekly nab-paclitaxel with gemcitabine is associated with a lower cost, acceptable toxicity profile and appears to be relatively effective in pancreatic cancer. Prospective randomized studies confirming its potential benefits compared with standard weekly mGNabP are warranted.
BACKGROUND: Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is associated with significant toxicities, leading to a high rate of drug discontinuation. We implemented a modified regimen of gemcitabine and nab-paclitaxel (mGNabP) in an attempt to minimize toxicities while maintaining efficacy. METHODS: A total of 79 evaluable patients with metastatic pancreatic adenocarcinoma (mPC) treated with a modified regimen of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 15 of every 28-day cycle were identified from our prospective database. A total of 57 patients received this regimen as first-line treatment and were evaluated for toxicities, progression-free survival (PFS), and overall survival (OS). Overall, 22 patients with advanced or metastatic PC treated with the modified regimen outside the first-line setting were only evaluated for toxicities. RESULTS: The median OS and PFS were 10 months [95% confidence interval (CI) 5.9-13 months] and 5.4 months (95% CI 4.1-7.4 months) for patients that received the modified regimen as first-line therapy. Neurotoxicity occurred in 27% with only 1.6% of patients experiencing grade ⩾3 toxicity. The incidence of grade ⩾3 neutropenia was 19%, resulting in growth factor support in 12% of patients. This rate was similar in patients who received the modified regimen for first-line treatment of mPC versus the overall group. CONCLUSIONS: A modified regimen of biweekly nab-paclitaxel with gemcitabine is associated with a lower cost, acceptable toxicity profile and appears to be relatively effective in pancreatic cancer. Prospective randomized studies confirming its potential benefits compared with standard weekly mGNabP are warranted.
Entities:
Keywords:
efficacious; gemcitabine-improved toxicity; modified regimen; nab-paclitaxel; pancreatic cancer
Authors: A Gonçalves; M Gilabert; E François; L Dahan; H Perrier; R Lamy; D Re; R Largillier; M Gasmi; X Tchiknavorian; B Esterni; D Genre; L Moureau-Zabotto; M Giovannini; J-F Seitz; J-R Delpero; O Turrini; P Viens; J-L Raoul Journal: Ann Oncol Date: 2012-07-05 Impact factor: 32.976
Authors: Thierry Conroy; Françoise Desseigne; Marc Ychou; Olivier Bouché; Rosine Guimbaud; Yves Bécouarn; Antoine Adenis; Jean-Luc Raoul; Sophie Gourgou-Bourgade; Christelle de la Fouchardière; Jaafar Bennouna; Jean-Baptiste Bachet; Faiza Khemissa-Akouz; Denis Péré-Vergé; Catherine Delbaldo; Eric Assenat; Bruno Chauffert; Pierre Michel; Christine Montoto-Grillot; Michel Ducreux Journal: N Engl J Med Date: 2011-05-12 Impact factor: 91.245
Authors: H Oettle; D Richards; R K Ramanathan; J L van Laethem; M Peeters; M Fuchs; A Zimmermann; W John; D Von Hoff; M Arning; H L Kindler Journal: Ann Oncol Date: 2005-08-08 Impact factor: 32.976
Authors: Volker Heinemann; Detlef Quietzsch; Frank Gieseler; Michael Gonnermann; Herbert Schönekäs; Andreas Rost; Horst Neuhaus; Caroline Haag; Michael Clemens; Bernard Heinrich; Ursula Vehling-Kaiser; Martin Fuchs; Doris Fleckenstein; Wolfgang Gesierich; Dirk Uthgenannt; Hermann Einsele; Axel Holstege; Axel Hinke; Andreas Schalhorn; Ralf Wilkowski Journal: J Clin Oncol Date: 2006-08-20 Impact factor: 44.544
Authors: Giuseppe Colucci; Roberto Labianca; Francesco Di Costanzo; Vittorio Gebbia; Giacomo Cartenì; Bruno Massidda; Elisa Dapretto; Luigi Manzione; Elena Piazza; Mirella Sannicolò; Marco Ciaparrone; Luigi Cavanna; Francesco Giuliani; Evaristo Maiello; Antonio Testa; Paolo Pederzoli; Massimo Falconi; Ciro Gallo; Massimo Di Maio; Francesco Perrone Journal: J Clin Oncol Date: 2010-03-01 Impact factor: 44.544
Authors: Philip A Philip; Jacqueline Benedetti; Christopher L Corless; Ralph Wong; Eileen M O'Reilly; Patrick J Flynn; Kendrith M Rowland; James N Atkins; Barry C Mirtsching; Saul E Rivkin; Alok A Khorana; Bryan Goldman; Cecilia M Fenoglio-Preiser; James L Abbruzzese; Charles D Blanke Journal: J Clin Oncol Date: 2010-07-06 Impact factor: 44.544
Authors: M Cantore; G Fiorentini; G Luppi; G Rosati; R Caudana; E Piazza; G Comella; C Ceravolo; L Miserocchi; A Mambrini; A Del Freo; D Zamagni; C Rabbi; M Marangolo Journal: J Chemother Date: 2004-12 Impact factor: 1.714
Authors: Andrew H Ko; Jeanne M Quivey; Alan P Venook; Emily K Bergsland; Elizabeth Dito; Brian Schillinger; Margaret A Tempero Journal: Int J Radiat Oncol Biol Phys Date: 2007-03-23 Impact factor: 7.038
Authors: Daniel D Von Hoff; Thomas Ervin; Francis P Arena; E Gabriela Chiorean; Jeffrey Infante; Malcolm Moore; Thomas Seay; Sergei A Tjulandin; Wen Wee Ma; Mansoor N Saleh; Marion Harris; Michele Reni; Scot Dowden; Daniel Laheru; Nathan Bahary; Ramesh K Ramanathan; Josep Tabernero; Manuel Hidalgo; David Goldstein; Eric Van Cutsem; Xinyu Wei; Jose Iglesias; Markus F Renschler Journal: N Engl J Med Date: 2013-10-16 Impact factor: 91.245
Authors: Justin C Tossey; Joshua Reardon; Jeffrey B VanDeusen; Anne M Noonan; Kyle Porter; Matthew J Arango Journal: Med Oncol Date: 2019-09-07 Impact factor: 3.064
Authors: Danielle C Glassman; Randze L Palmaira; Christina M Covington; Avni M Desai; Geoffrey Y Ku; Jia Li; James J Harding; Anna M Varghese; Eileen M O'Reilly; Kenneth H Yu Journal: BMC Cancer Date: 2018-06-27 Impact factor: 4.430
Authors: Adam R Wolfe; Dhivya Prabhakar; Vedat O Yildiz; Jordan M Cloyd; Mary Dillhoff; Laith Abushahin; Dayssy Alexandra Diaz; Eric D Miller; Wei Chen; Wendy L Frankel; Anne Noonan; Terence M Williams Journal: Cancer Med Date: 2020-05-16 Impact factor: 4.452