Literature DB >> 23077684

A phase I study of cetuximab in combination with gemcitabine and radiation for locally advanced pancreatic cancer.

A Bapsi Chakravarthy1, Chiao Jillian Tsai, Nathan O'Brien, A Craig Lockhart, Emily Chan, Alexander Parikh, Jordan D Berlin, Nipun Merchant.   

Abstract

BACKGROUND: Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). The primary goal of this phase I study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine when combined with cetuximab plus radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Patients with locally unresectable adenocarcinoma of the pancreas were treated with gemcitabine (200 mg/m(2)/week before dose escalation) plus cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) concurrent with radiation (50.4 Gy).
RESULTS: Nine patients were enrolled in the study. One withdrew due to declining performance status before receiving any therapy. Grade 4 allergic reactions to cetuximab caused the withdrawal of 2 patients. Another patient had elevated liver function test results and a stroke after his loading dose of cetuximab. Grade 3 or 4 toxicity developed in 3 of the remaining 5 patients treated with the level 1 dose. Therefore, no further dose escalations were planned. Grade 3 toxicities included nausea, vomiting, ileus, and pneumonitis. One patient had grade 4 diarrhea.
CONCLUSIONS: The combination of cetuximab, gemcitabine, and radiation resulted in significant toxicity. A recommended phase II dose could not be determined.

Entities:  

Year:  2012        PMID: 23077684      PMCID: PMC3433259     

Source DB:  PubMed          Journal:  Gastrointest Cancer Res        ISSN: 1934-7820


  22 in total

1.  Phase I study of anti--epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer.

Authors:  F Robert; M P Ezekiel; S A Spencer; R F Meredith; J A Bonner; M B Khazaeli; M N Saleh; D Carey; A F LoBuglio; R H Wheeler; M R Cooper; H W Waksal
Journal:  J Clin Oncol       Date:  2001-07-01       Impact factor: 44.544

2.  Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma.

Authors:  R A Wolff; D B Evans; D M Gravel; R Lenzi; P W Pisters; J E Lee; N A Janjan; C Charnsangavej; J L Abbruzzese
Journal:  Clin Cancer Res       Date:  2001-08       Impact factor: 12.531

3.  Phase I study of weekly gemcitabine as a radiation sensitizer for unresectable pancreatic cancer.

Authors:  Matthew M Poggi; Glenn S Kroog; Angelo Russo; Christine Muir; John Cook; Judith Smith; James B Mitchell; Laurie L Herscher
Journal:  Int J Radiat Oncol Biol Phys       Date:  2002-11-01       Impact factor: 7.038

4.  Epidermal growth factor receptor blockade by antibody IMC-C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice.

Authors:  J P Overholser; M C Prewett; A T Hooper; H W Waksal; D J Hicklin
Journal:  Cancer       Date:  2000-07-01       Impact factor: 6.860

5.  Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer.

Authors:  C J McGinn; M M Zalupski; I Shureiqi; J M Robertson; F E Eckhauser; D C Smith; D Brown; G Hejna; M Strawderman; D Normolle; T S Lawrence
Journal:  J Clin Oncol       Date:  2001-11-15       Impact factor: 44.544

6.  EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

Authors:  J Guillermo Paez; Pasi A Jänne; Jeffrey C Lee; Sean Tracy; Heidi Greulich; Stacey Gabriel; Paula Herman; Frederic J Kaye; Neal Lindeman; Titus J Boggon; Katsuhiko Naoki; Hidefumi Sasaki; Yoshitaka Fujii; Michael J Eck; William R Sellers; Bruce E Johnson; Matthew Meyerson
Journal:  Science       Date:  2004-04-29       Impact factor: 47.728

7.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

Authors:  Thomas J Lynch; Daphne W Bell; Raffaella Sordella; Sarada Gurubhagavatula; Ross A Okimoto; Brian W Brannigan; Patricia L Harris; Sara M Haserlat; Jeffrey G Supko; Frank G Haluska; David N Louis; David C Christiani; Jeff Settleman; Daniel A Haber
Journal:  N Engl J Med       Date:  2004-04-29       Impact factor: 91.245

8.  Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha.

Authors:  M Korc; B Chandrasekar; Y Yamanaka; H Friess; M Buchier; H G Beger
Journal:  J Clin Invest       Date:  1992-10       Impact factor: 14.808

9.  Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.

Authors:  C Almoguera; D Shibata; K Forrester; J Martin; N Arnheim; M Perucho
Journal:  Cell       Date:  1988-05-20       Impact factor: 41.582

10.  A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer.

Authors:  M Ikeda; S Okada; K Tokuuye; H Ueno; T Okusaka
Journal:  Br J Cancer       Date:  2002-05-20       Impact factor: 7.640

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  5 in total

Review 1.  Developing effective combination therapy for pancreatic cancer: An overview.

Authors:  Aubrey L Miller; Patrick L Garcia; Karina J Yoon
Journal:  Pharmacol Res       Date:  2020-03-02       Impact factor: 7.658

2.  Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study.

Authors:  Agata I Rembielak; Pooja Jain; Andrew S Jackson; Melanie M Green; Gillian R Santorelli; Gillian A Whitfield; Adrian Crellin; Angel Garcia-Alonso; Ganesh Radhakrishna; James Cullen; M Ben Taylor; Ric Swindell; Catharine M West; Juan Valle; Azeem Saleem; Patricia M Price
Journal:  Transl Oncol       Date:  2014-02-01       Impact factor: 4.243

3.  Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors.

Authors:  Yuichi Ando; Megumi Inada-Inoue; Ayako Mitsuma; Takayuki Yoshino; Atsushi Ohtsu; Naoko Suenaga; Masahiko Sato; Tomoyuki Kakizume; Matthew Robson; Cornelia Quadt; Toshihiko Doi
Journal:  Cancer Sci       Date:  2014-02-13       Impact factor: 6.716

4.  Anti-pancreatic cancer deliverables from sea: first-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae.

Authors:  Sheeja Aravindan; Caroline R Delma; Somasundaram S Thirugnanasambandan; Terence S Herman; Natarajan Aravindan
Journal:  PLoS One       Date:  2013-04-16       Impact factor: 3.240

5.  Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer.

Authors:  Michele Fiore; Lucio Trodella; Sergio Valeri; Domenico Borzomati; Barnaba Floreno; Edy Ippolito; Pasquale Trecca; Luca Eolo Trodella; Rolando Maria D'Angelillo; Sara Ramella; Roberto Coppola
Journal:  Radiat Oncol       Date:  2015-12-15       Impact factor: 3.481

  5 in total

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