| General information |
| Database: | DB00428 |
| Objective: | Preoperative chemoradiotherapy (CRT) improves outcomes in patients with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this patient group with a primary end point of a pathologic complete response (pCR) more than and equal to 35%. |
| Authors: | Lockhart AC, et al |
| Title: | Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051). |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 24562448 |
| Trial Design |
| Clinical Trial Id: | NCT00757172 |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the distal esophagus or GEJ (Sietheyrt I or II), (iv) clinical stage (AJCC 6th edition) of T3N0M0, T2/3N1M0, or T23N0/1M1a (by EUS, CT, and PET staging) |
| Therapy Type: | com |
| Therapeutic Combination Type: | 6 |
| Therapeutic Combination Content: | neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery |
| Study Type: | phase II study |
| Key Patients Feature: | Treatment na ve patients met the following inclusion criteria: (i) age more than and equal to 18years, (ii) ECOG/Zubrod Performance Status 0-1, (iii) biopsyproven resectable adenocarcinoma of the distal esophagus or GEJ (Sietheyrt I or II), (iv) clinical stage (AJCC 6th edition) of T3N0M0, T2/3N1M0, or T23N0/1M1a (by EUS, CT, and PET staging), (v) no evidence of distant metastases, (vi) no grade more than and equal to 2 peripheral neuropathy, (vii) adequate bone marrow, hepatic, and renal function, (viii) no prior invasive malignancy unlessdiseasefree for >5 years, (ix) nonpregnant and nonbreast feeding, (x) noprior chest or upper abdomen RT; prior therapy with docetaxel, cisplatin orantiEGFR therapy; or prior esophageal or gastric surgery (except antireflux), (xi) no interstitial lung disease, and (xii) no medical or psychiatricabnormality that might affect study participation. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received docetaxel (40 mg/m(2)), cisplatin (40 mg/m(2)), and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, and 9 with RT (5040 cGy, 180 cGy/day ¡Á 28 days) beginning week 5. Resection was planned after completing CRT. PCR was defined as no viable residual tumor cells. |
| Primary End Point: | the proportion of patients with pCR following surgery. |
| Secondary End Point: | NA |
| Patients Number: | 70 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | No response:11.1%, Partial response:35.1%, Nearcomplete response (<10% viable cells):20.4%, Complete response:33.3% |
| Disease Control Rate: | 0.73 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 19.4 months and 3year overall survival was 38.6% (95% confidence interval 24.5% to 60.8%). |
| Adverse Event(agent arm): | 48.5% had toxicity more than and equal to grade 4. Lymphopenia (43%) was most common. Operative mortality was 3.7%. Adult respiratory distress syndrome was encountered in two patients (3.7%). |
| Conclusions: | Neoadjuvant CRT with DCP is active (pCR + nearpCR = 53.7%) but toxicity is significant. Further evaluation of this regimen in an unselected population is not recommended. |