| General information |
| Database: | DB00416 |
| Objective: | To determine the maximum tolerated dose (MTD) and doselimiting toxicities (DLTs) of concurrent chemoradiotherapy and cetuximab in patients with nonresectable locally advanced esophageal cancer. |
| Authors: | Holl nder C, et al |
| Title: | a phase I study of concurrent chemoradiotherapy and cetuximab for locally advanced esophageal cancer. |
| Journal: | Anticancer Res. |
| Year: | 2012 |
| PMID: | 22993353 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced carcinoma of the esophagus or GEJ |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | concurrent chemoradiotherapy and cetuximab |
| Study Type: | phase I dose escalating trial |
| Key Patients Feature: | Patients with histologically for confirmed nonresectableand locally advanced carcinoma of the esophagus or GEJ, Sietheyrttype 1 and 2, were eligible. Operable patients who had declinedsurgery were also eligible treatment. Other inclusion criteriaincluded measurable disease assessed by RECIST version 1.0, agebetween 18 and 75 years, life expectancy of more than threemonths, WHO performance status (PS) 02, and adequate bonemarrow, hepatic, and renal functions |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Escalating doses of oxaliplatin every second week and daily tegafur/uracil were given concurrently with radiotherapy, 59.4 Gy in 33 fractions. Cetuximab was given on day 15 (400 mg/m(2)) and weekly (250 mg/m(2)) during radiotherapy. Fixed doses of oxaliplatin (130 mg/m(2)) and tegafur/uracil (300 mg/m(2)) were administered before, and after radiotherapy. |
| Primary End Point: | the maximum tolerated dose (MTD) and doselimiting toxicity (DLT). |
| Secondary End Point: | toxicity, response according to RECIST version 1.0, timetoprogression (TTP), and overall survival (OS). |
| Patients Number: | 11 |
| Trial Results |
| DLT_MTD: | DLTs were defined as febrile neutropenia more than and equal to grade 3, or haematologic toxicity more than and equal to grade 4, or nonhaematologic toxicity more than and equal to grade 3 except skin reaction, alopecia and adequately treated nausea and vomiting. In DL2 (tegafur/uracil 300 mg/m(2), oxaliplatin 30 mg/m(2)) two grade 3/4 fistula and one grade 3 neuropathy were observed. Six patients were enrolled in DL1 (tegafur/uracil 150 mg/m(2)/, oxaliplatin 30 mg/m(2)) with no DLTs.DL1 was established as the MTD. |
| Objective Response Rate: | Response evaluation was performed according to RECIST 1.0 criteria on day 196. Four out of 9 patients had radiological complete response (CR) (Table IV). Notably, one of these had pathological CR (pCR) after surgery. One patient progressed during therapy, and two patients died during followup of cancer prior to response evaluation. One patient died before receiving the last fixed dose of oxaliplatin and tegafur/uracil. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9.2 months (95% CI 0.4 17.9) |
| Median OS A vs. C: | 13.2 months (95% CI 5.3 >21) |
| Adverse Event(agent arm): | No grade 3 or grade 4 myelotoxicity was observed. Cetuximabinduced skin rash was observed as expected to maximum grade 2, with no worsening during radiotherapy. Two patients (one in DL 1 and one in DL 2) theynt off study on day 15 due to grade 3 and 4 allergic reactions to cetuximab. The first patient, on DL 1, developed a rash after the infusion of approximately 50 mg of cetuximab and subsequently suffered a cardiac arrest. |
| Conclusions: | Concomitant chemoradiotherapy and cetuximab had significant activity. DL1 was established as the MTD. |