| General information |
| Database: | DB00402 |
| Objective: | 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/gastrooesophageal 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. |
| Authors: | Wainberg ZA, et al |
| Title: | Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastrooesophageal junction. |
| Journal: | Br J Cancer |
| Year: | 2011 |
| PMID: | 21811258 |
| Trial Design |
| Clinical Trial Id: | NCT00591123 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced adenocarcinoma of the esophagus and gastrooesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | modified FOLFOX6 and erlotinib |
| Study Type: | adenocarcinoma of theoesophagus or GEJ |
| Key Patients Feature: | Patients with a histologic diagnosis of adenocarcinoma of theoesophagus or GEJ with measurable disease by Response EvaluationCriteria in Solid Tumours (RECIST) were considered eligible for thetrial. In this study, oesophagus and GEJ tumours were defined by theSietheyrt classification (Sietheyrt class I, II and III), which includedcancers arising within 5 cm of the anatomic GE junction (distaloesophagus) or from the gastric cardia (Sietheyrt and Stein, 1998).Only patients with previously untreated metastatic disease wereincluded. Previous radiotherapy or adjuvant chemotherapy waspermitted as long as no treatment was received in the previous12 months. Other eligibility requirements included ECOG performance status of 0 or 1, peripheral neuropathy pgrade 1, the abilityto swallow oral medications, adequate haematologic (absoluteneutrophil count 41500 mm - 3, platelets4100 000 mm - 3), renal(creatinine clearance 460 ml min - 1) and hepatic function (totalbilirubinp1.5 ULN, AST and ALTp3.0 ULN or p5.0 ULN ifthere is liver metastasis). |
| Biomarker: | KRAS mutations, EGFR mutation and human epidermal growth factor receptor 2 amplification |
| Biomark Analysis: | The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and human epidermal growth factor receptor 2 amplification (19%). |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with oxaliplatin 85 mg m(2), 5FU 400 mg m(2), LV 400 mg m(2) on day 1, 5FU 2400 mg m(2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. |
| Primary End Point: | RR, toxicity, PFS, OS and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptordependent pathways. |
| Secondary End Point: | NA |
| Patients Number: | 33 |
| Trial Results |
| DLT_MTD: | The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) andperipheral neuropathy (8% |
| Objective Response Rate: | there were two complete responses, 15 partial responses for an objectiveRR 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). |
| Disease Control Rate: | 0.512 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.5 months (95% CI, 3.1-7.5 months) |
| Median OS A vs. C: | 11.0 months (95% CI, 8.0-17.4 months). |
| Adverse Event(agent arm): | The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). |
| Conclusions: | In patients with EsoGEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ¡À erlotinib could be considered for further development. |