Gefitinib/Gemcitabine Better Tolerated Than Gefitinib/Vinorelbine by Elderly Patients With Advanced NSCLC

TORINO, Italy-Combinationtherapy with gefitinib (Iressa) andgemcitabine (Gemzar) produced diseasecontrol in 45.7% of elderly patientswith advanced non-small-celllung cancer (NSCLC), according toGiorgio V. Scagliotti, MD, of the Universityof Turin, Torino, Italy, reportingresults of a phase II Italianmulticenter study (abstract 7081). Thestudy also found that patients werebetter able to tolerate gefitinib/gemcitabinethan a gefitinib/vinorelbine(Navelbine) combination.The study included 59 elderly patientswith chemonaive stage IIIB/IVNSCLC. All patients were treated withgefitinib (250 mg/day orally until progression),plus either vinorelbine(30 mg/m² IV, arm A) or gemcitabine(1,200 mg/m² IV, arm B). For unexplainedreasons, the two study armsdiffered in a number of characteristics.Male patients accounted for 58%of arm A vs 80% of arm B, and squamoushistology characterized 17% ofarm A vs 31% of arm B.

Drugs were given on days 1 and 8every 21 days for six cycles. The primaryendpoint was response rate.Arm A was closed after 21 of thefirst 24 patients (87.5%) had grade 3or 4 adverse events, Dr. Scagliotti reported. These included 72% grade 3or 4 neutropenia and treatment-relateddeaths (one sudden cardiac arrest,one grade 4 neutropenia with septicshockand cerebral infarction, and onegrade 4 diarrhea followed by cardiacarrest)."Of the 12 nonevaluable patients, 6had withdrawn from the study, 5 haddied, and 1 had an unconfirmed diagnosisof NSCLC," Dr. Scagliotti said.In both arms, the most commongefitinib-related adverse event was skintoxicity, mainly grade 1-2. In arm B,11.4% of patients experienced grade 3-4 neutropenia and 8.6% had thrombocytopenia, compared with 0 in arm A.Grade 3-4 asthenia and diarrhea weremore common in arm A, with boththose adverse events occurring among12% in arm A vs 5.7% in arm B. Dr.Scagliotti also reported one case of grade4 elevated transaminase levels.Responses and DurationAmong the 27 patients in arm A(gefitinib/vinorelbine) 1 (4%) had acomplete response (CR), 3 (12%) hadpartial responses (PR), 7 (28%) hadstable disease (SD), 6 had progressivedisease (PD), and 7 patients were notevaluable (see Table 1). Median durationof response on arm A was 274days; median time to progression(TTP) was 91 days; median survivalwas 371 days; and 63% of patientswere alive at 6 months.Responses and DurationAmong the 27 patients in arm A(gefitinib/vinorelbine) 1 (4%) had acomplete response (CR), 3 (12%) hadpartial responses (PR), 7 (28%) hadstable disease (SD), 6 had progressivedisease (PD), and 7 patients were notevaluable (see Table 1). Median durationof response on arm A was 274days; median time to progression(TTP) was 91 days; median survivalwas 371 days; and 63% of patientswere alive at 6 months."In elderly patients with advancedNSCLC, vinorelbine plus gefitinib wasactive but toxicity was unacceptable,while gemcitabine plus gefitinib wassafe, and a remarkable percentage ofpatients achieved disease control," Dr.Scagliotti concluded.