Cetuximab Is Safe Addition to Induction Chemo : In small study, most patients with head and neck cancer show complete clinical response to regimen.


CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.


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