| General information |
| Database: | DB00289 |
| Objective: | Platinumbased therapy is active in advanced head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis; many have difficulty tolerating cisplatinbased regimens. Oxaliplatin has antitumor activity without many of the toxicities of cisplatin. They conducted a phase I pilot study to investigate the dose limitation. |
| Authors: | Clark JI, et al |
| Title: | Phase I pilot study of oxaliplatin, infusional 5FU, and cetuximab in recurrent or metastatic head and neck cancer. |
| Journal: | Med Oncol. |
| Year: | 2013 |
| PMID: | 23266940 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | Cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | oxaliplatin, infusional 5FU+ cetuximab |
| Study Type: | a phase I pilot study |
| Key Patients Feature: | Patients who were more than and equal to 18 years of age with untreated recurrent or metastatic pathologically confirmed HNSCC were eligible for participation. Primary sites allowed included oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, sinus, and unknown primary. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The planned dose escalation schedule included: dose level 1: oxaliplatin 100 mg/m(2) day 1, 5FU CIV 750 mg/m(2)/day over 96 h beginning day 1, and cetuximab 400 mg/m(2) day 1 (then 250 mg/m(2) weekly) every 21 days. Dose level 2: oxaliplatin 130 mg/m(2) day 1, 5FU CIV 1, 000 mg/m(2)/day over 96 h beginning day 1, and the same dose and schedule of cetuximab. |
| Primary End Point: | the safety and tolerability of escalating doses of the combination |
| Secondary End Point: | clinical responses |
| Patients Number: | 10 |
| Trial Results |
| DLT_MTD: | Dose level 1 toxicity included grade 12 stomatitis, fatigue, acneiform rash, and anemia, and grade 1 nausea and transaminitis. Dose level 2 toxicity was unacceptable: 2 of 3 patients experienced grade 4 toxicities (stomatitis, diarrhea, and acute renal failure) requiring hospitalization with one treatmentrelated death. Accrual was therefore closed with dose level 1 considered the maximum tolerated dose. |
| Objective Response Rate: | one complete response and two partial responses were observed in three of the patients enrolled onto dose level one. One patient experienced what they are calling a minor response (less than a partial response) on dose level two. Two patients experienced stable disease as their best observed response. All responses observed were shortlived, lasting 3-4 months. No patients enrolled remain alive, with an average overall survival of just over 5 months. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 5 months |
| Adverse Event(agent arm): | as shown in the DLTs |
| Conclusions: | The regimen of oxaliplatin 100 mg/m(2) day 1, infusional 5FU 750 mg/m(2)day over 96 h beginning day 1, and cetuximab 400 mg/m(2) day 1 (then 250 mg/m(2) weekly), every 21 days, has manageable toxicity; these doses are recommended forphase II evaluation in the treatment for unresectable or metastatic HNSCC. |