Erlotinib Shows Early Activity in Combination Therapy for Head and Neck Cancer

HOUSTON-Combining erlotinib(Tarceva) with chemotherapyfor advanced head and neck cancerappears to boost response rates, accordingto early findings from a smallphase II study. After two cycles oftherapy with cisplatin , docetaxel (Taxotere),and erlotinib, 96% of patientsin this trial had tumor shrinkage orstable disease, said Edward Kim, MD,and colleagues at The University ofTexas M.D. Anderson Cancer Centerin Houston. Dr. Kim, an assistant professorin the division of thoracic/head& neck medical oncology, presentedthe results (abstract 5546).By comparison, in other trials insmall cell carcinoma of the head andneck (SCCHN), patients treated withcisplatin and docetaxel have had a responserate of 40% and erlotinib as asingle agent has yielded a responserate of 4.3%.This ongoing study includes patientswith metastatic or recurrentSCCHN who have had no prior EGFRtargetedtherapy. Participants mayhave had one prior chemotherapy regimenbut not for metastatic or recurrentdisease. They receive cisplatin anddocetaxel every 3 weeks and erlotinibdaily.Interim ResultsWith 27 of a planned 50 patientsenrolled, the investigators were able toreport on 22 evaluable patients whohad completed two cycles of therapy.Three patients had a complete response,14 had a partial response, andfour had stable disease, for an "overalldisease control rate" of 96%.Other toxicities associated with thechemotherapy/erlotinib combinationhave been manageable, the investigatorsreported; six patients had grade 3neutropenia and one had grade 4 fe-brile neutropenia. The most commongrade 1 and 2 toxicities have beendiarrhea, nausea, and rash.EGFR is overexpressed in 80% to90% of HNSCC tumors. The investigatorsplan to look for biomarkers inthe EGFR signaling pathway, such asphosphorylated Akt, MEK, and K-ras,that may correlate with response tothis regimen. EGRF mutations havenot been found in head and neck cancers,Dr. Kim said, but the investigatorswill look for other EGFR-relatedbiomarkers, such as gene copy number.If the response data continue tohold up, he said, the next step could bea phase III trial with patients randomizedto receive either cisplatin anddocetaxel alone or cisplatin and docetaxelwith erlotinib. A neoadjuvantregimen could also be considered, Dr.Kim said.Testing a TreatmentAlgorithm for RashIn this trial, Dr. Kim and colleaguesare also testing a prospective treatmentalgorithm for rash, a commonand sometimes serious adverse eventassociated with erlotinib and othertyrosine kinase inhibitors. The algorithmincludes topical and oral antibioticsand steroids in different combinationsand at different levels,depending on the type and severity ofthe rash. Of the 16 patients who hadreceived treatment for rash at the timeof Dr. Kim's presentation, most hadresponded either completely or partially.