PMID- 24114668 OWN - NLM STAT- MEDLINE DCOM- 20140116 LR - 20201209 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 119 IP - 23 DP - 2013 Dec 1 TI - Intermittent versus continuous erlotinib with concomitant modified "XELOX" (q3W) in first-line treatment of metastatic colorectal cancer: correlation with serum amphiregulin and transforming growth factor alpha. PG - 4145-53 LID - 10.1002/cncr.28327 [doi] AB - BACKGROUND: This study evaluated the activity of 2 schedules of erlotinib in combination with chemotherapy, and the prognostic significance of serum amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic colorectal cancer. METHODS: A total of 60 untreated patients were randomized to a "continuous" (CON; erlotinib 100 mg daily) or an "intermittent" (INT; erlotinib 150 mg on alternate day on day 2 to 14, then 150 mg daily on days 15 to 21) schedule of erlotinib with a modified XELOX (capecitabine plus oxaliplatin) regimen. Serum levels of AREG and TGFa were determined serially. RESULTS: Baseline characteristics were similar between the 2 arms. Of the 58 patients evaluated for response, there was a nonsignificant trend toward a slightly higher overall response rate in the INT arm (66.7%) versus the CON arm (56.7%). At a median follow-up of 2.8 years, the median overall survival was 18.8 months (95% confidence interval = 11.3-22.9 months) and 20.7 months (95% confidence interval = 12.5-31 months, P = .19) for the CON and INT arm, respectively. KRAS mutation did not predict drug response. The 2 arms did not differ significantly in toxicity. Baseline serum TGFa was an independent predictor of progression-free survival, whereas a drop in serum TGFa and AREG levels following 3 to 4 cycles of treatment were associated with shorter progression-free survival and overall survival, respectively. CONCLUSIONS: The intermittent erlotinib schedule was associated with a higher response rate, although this is not statistically significant. Serum TGFa and AREG levels have prognostic significance in erlotinib-treated patients with colorectal cancer, and further studies are warranted. CI - (c) 2013 American Cancer Society. FAU - Ma, Brigette B Y AU - Ma BB AD - Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, State Key Laboratory in Oncology in South China, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Chan, Stephen L AU - Chan SL FAU - Ho, Wing M AU - Ho WM FAU - Lau, Wilson AU - Lau W FAU - Mo, Frankie AU - Mo F FAU - Hui, Edwin P AU - Hui EP FAU - Chan, Charles AU - Chan C FAU - Poon, Annette AU - Poon A FAU - Dattatray, Rasalkar D AU - Dattatray RD FAU - Wong, S C Cesar AU - Wong SC FAU - To, Ka F AU - To KF FAU - King, Ann D AU - King AD FAU - Ahuja, Anil AU - Ahuja A FAU - Chan, Anthony T C AU - Chan AT LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20131001 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (EGF Family of Proteins) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (KRAS protein, human) RN - 0 (Oxaloacetates) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Quinazolines) RN - 0 (Transforming Growth Factor alpha) RN - 0W860991D6 (Deoxycytidine) RN - 6804DJ8Z9U (Capecitabine) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) RN - EC 3.6.5.2 (ras Proteins) RN - U3P01618RT (Fluorouracil) RN - XELOX SB - IM MH - Adult MH - Aged MH - Amphiregulin MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Capecitabine MH - Colorectal Neoplasms/*drug therapy/mortality MH - Deoxycytidine/administration & dosage/*analogs & derivatives MH - Drug Administration Schedule MH - EGF Family of Proteins MH - Erlotinib Hydrochloride MH - Female MH - Fluorouracil/administration & dosage/*analogs & derivatives MH - Glycoproteins/*blood MH - Humans MH - Intercellular Signaling Peptides and Proteins/*blood MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Metastasis MH - Oxaloacetates MH - Patient Compliance MH - Prognosis MH - Protein Kinase Inhibitors/*administration & dosage MH - Proto-Oncogene Proteins/genetics MH - Proto-Oncogene Proteins p21(ras) MH - Quinazolines/*administration & dosage/toxicity MH - Transforming Growth Factor alpha/*blood MH - ras Proteins/genetics OTO - NOTNLM OT - amphiregulin OT - capecitabine OT - erlotinib OT - oxaliplatin OT - transforming growth factor alpha EDAT- 2013/10/12 06:00 MHDA- 2014/01/17 06:00 CRDT- 2013/10/12 06:00 PHST- 2013/04/25 00:00 [received] PHST- 2013/06/09 00:00 [revised] PHST- 2013/07/16 00:00 [accepted] PHST- 2013/10/12 06:00 [entrez] PHST- 2013/10/12 06:00 [pubmed] PHST- 2014/01/17 06:00 [medline] AID - 10.1002/cncr.28327 [doi] PST - ppublish SO - Cancer. 2013 Dec 1;119(23):4145-53. doi: 10.1002/cncr.28327. Epub 2013 Oct 1.