Phase II clinical trial of h-R3 combined with radiotherapy in locally advanced nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to evaluate the short- and long-term efficacy and toxicity of the humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody h-R3 when combined with radiotherapy for the treatment of locally advanced nasopharyngeal carcinoma (NPC). METHODS: 35 patients with stage III-IVb NPC with moderate- or strong-intensity EGFR expression were randomly divided into either a radiotherapy alone group or a group receiving radiotherapy combined with h-R3. RESULTS: The complete remission (CR) rates of the combination group at three time points were significantly higher (p<0.05) than those of the radiotherapy alone group. Overall survival, 3-year local control rate, and no distant metastasis rate did not differ between the two groups. No severe toxicity was noticed. CONCLUSION: h-R3 is an agent with good safety profile which could help enhance the radiation antitumor effect in locally advanced NPC, but it did not seem to exhibit significant long-term efficacy.

[Phase II clinical trial of h-R3 combined radiotherapy for locoregionally advanced nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are easily to produce human anti-murine antibody response at present clinical use. This may influence therapeutic effect. This study was to evaluate the short-term and long-term efficacy and toxicity of the humanized anti-EGFR monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: Patients with newly diagnosed stage III-IVb (UICC 1997) NPC, who had moderate or strong EGFR expression, were randomized into radiotherapy alone group or radiotherapy combined h-R3 group. Similar dosage and technique of radiotherapy was administered in both groups. The combination group received weekly intravenous infusion of 100 mg h-R3 during radiotherapy. The short-term efficacy was evaluated according to WHO criteria. The survival was analyzed by Kaplan-Meier method. RESULTS: A total of 35 patients were enrolled, 17 in radiotherapy alone group and 18 in combination group. During treatment, only 1 patient withdrew from the combination group. The overall complete remission (CR) rates at the end of treatment, 5 and 17 weeks after treatment were significantly higher in combination group than in radiotherapy alone group (72.2% vs. 35.3%, 83.3% vs. 41.2%, and 83.3% vs. 47.1%, P<0.05). Median follow-up time was 31.9 months (range, 4.2-40.7 months). No significant differences in 3-year locoregional control, distant metastasis-free survival and overall survival rates between the 2 groups were found. Except for 1 patient suffered from grade 2 vomiting, no patient developed other adverse events in combination group. No significant differences in radiotherapy-related adverse events between the 2 groups were observed. CONCLUSIONS: h-R3 is a safe drug which may enhance the response of advanced NPC patients to radiotherapy. However, h-R3 seems not to significantly affect the long-term outcomes.

[Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. METHODS: Totally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy. RESULTS: Of the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group. CONCLUSION: This phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.