Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction - PubMed (original) (raw)

Clinical Trial

. 2011 Sep 6;105(6):760-5.

doi: 10.1038/bjc.2011.280. Epub 2011 Aug 2.

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Clinical Trial

Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction

Z A Wainberg et al. Br J Cancer. 2011.

Abstract

Background: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers.

Methods: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(-2), 5-FU 400 mg m(-2), LV 400 mg m(-2) on day 1, 5-FU 2400 mg m(-2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways.

Results: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5-68.6%). Median PFS was 5.5 months (95% CI, 3.1-7.5 months) and median OS was 11.0 months (95% CI, 8.0-17.4 months). The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%).

Conclusion: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ± erlotinib could be considered for further development.

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Figure 1

Progression-free survival (PFS) and overall survival (OS) (Kaplan–Meier estimates).

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References

    1. Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jager E (2008) Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 26(9): 1435–1442 - PubMed
    1. Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, Di Fiore PP, Kraus MH (1995) Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 10(9): 1813–1821 - PubMed
    1. Altiok S, Mezzadra H, Jagannath S, Tsottles N, Rudek MA, Abdallah N, Berman D, Forastiere A, Gibson MK (2010) A novel pharmacodynamic approach to assess and predict tumor response to the epidermal growth factor receptor inhibitor gefitinib in patients with esophageal cancer. Int J Oncol 36(1): 19–27 - PMC - PubMed
    1. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10): 1626–1634 - PubMed
    1. Arber N, Shapira I, Ratan J, Stern B, Hibshoosh H, Moshkowitz M, Gammon M, Fabian I, Halpern Z (2000) Activation of c-K-ras mutations in human gastrointestinal tumors. Gastroenterology 118(6): 1045–1050 - PubMed

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