A. Garin

Phase III Study of Gefitinib Compared With Intravenous Methotrexate for Recurrent Squamous Cell Carcinoma of the Head and Neck

PURPOSE To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate. PATIENTS AND METHODS Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral gefitinib 250 mg/day, gefitinib 500 mg/day, or methotrexate 40 mg/m(2) intravenously weekly. Primary end point was overall survival, secondary end points were objective response rate (ORR), safety, symptom improvement, and quality of life (QOL). Exploratory end points included association of efficacy with epidermal growth factor receptor gene copy number and other biomarkers. RESULTS Neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate (hazard ratio [HR], 1.22; 95% CI, 0.95 to 1.57; P = .12; and HR, 1.12; 95% CI, 0.87 to 1.43; P = .39, respectively). In the gefitinib 250 mg/day, 500 mg/day, and methotrexate groups, respectively, median overall survival was 5.6, 6.0, and 6.7 months; ORRs (Response Evaluation Criteria in Solid Tumors) were 2.7%, 7.6% and 3.9%, with no statistically significant difference between either gefitinib arm and methotrexate. No unexpected adverse events were observed, except for tumor hemorrhage-type events with gefitinib (8.9%, gefitinib 250 mg/day; 11.4%, gefitinib 500 mg/day; 1.9%, methotrexate). QOL improvement rates (Functional Assessment of Cancer Therapy-Head & Neck total score) were 13.4%, 18.0%, and 6.0% for gefitinib 250 mg/day, 500 mg/day, and methotrexate, respectively. CONCLUSION In patients with recurrent or metastatic SCCHN, while responses with gefitinib were seen, neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate. With the exception of tumor hemorrhage-type events with gefitinib, the adverse event profiles were generally consistent with those previously observed.

Phase III Study of N,N-Diethyl-2-[4-(Phenylmethyl) Phenoxy]Ethanamine (BMS-217380-01) Combined With Doxorubicin Versus Doxorubicin Alone in Metastatic/Recurrent Breast Cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19

PURPOSE N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE; tesmilifene) is a novel agent that augments chemotherapy cytotoxicity in vitro and in vivo. A phase II trial combining DPPE and doxorubicin (DOX) in metastatic breast carcinoma showed increased response over that expected with DOX. We report a phase III trial comparing DOX with DPPE plus DOX in metastatic or recurrent breast cancer. PATIENTS AND METHODS Anthracycline-naive women with measurable metastatic disease were randomly assigned to receive, every 21 days, either DOX 60 mg/m(2) intravenously or DOX during the last 20 minutes of an 80-minute infusion of DPPE (5.3 mg/kg), in both cases to cumulative DOX doses of 450 mg/m(2). Patients receiving DPPE were aggressively premedicated to ameliorate toxicity. End points included progression-free survival (PFS), response rate (RR), and response duration (RD), quality of life (QOL), toxicity, and overall survival (OS). RESULTS A planned interim analysis failed to detect an RR difference more than 5%. The study was closed to additional accrual and all DPPE was discontinued. The final analysis was conducted as planned after 256 progression events (median follow-up, 20.5 months). There was no significant difference in RR, RD, or PFS between arms. DPPE plus DOX was statistically superior to DOX in OS (hazard ratio, 0.66; 95% CI, 0.48 to 0.91; P =.021). DPPE plus DOX was associated with more gastrointestinal and CNS toxicity. No consistent influence on QOL was detected. CONCLUSION This study demonstrated no advantage in RR, RD, or PFS but significantly superior OS for DPPE plus DOX. Additional studies of DPPE are warranted.

Chemotherapy efficacy and prognosis of patients with mediastinal seminoma. Single institution experience.

e16053Background: Patients with mediastinal nonseminomatous germ cell tumors belong to poor prognostic group by IGCCCG. Mediastinal seminoma is very rare disease and data of the prognosis and chemo...

The outcome differences between late and early relapses after orchiectomy (OE) in patients (pts) with stage I germ cell tumors (GCT).

e15013 Background: Late relapses (>2 years) after completion of chemotherapy are rare and often platinum-resistant. There are limited data concerning late relapses in chemotherapy-naïve pts with stage I GCT. This retrospective analysis was performed to compare the outcome between pts with stage I GCT, who had late (≥2 years) and early (≥3 months and < 2 years) relapse after OE. METHODS We analyzed data of 1069 CT-naïve pts with advanced GCT of testis treated in our department from 1986 to 2008. All pts had cisplatin- and etoposide-based CT. We identified 169 (15.8%) pts with prior stage I disease, who had not received adjuvant treatment: 140 and 29 pts had early and late relapse, respectively. Among pts with late relapse pure seminoma was revealed in 14 pts, nonseminoma - in 15 pts. Median f.-up time for 169 pts was 35 (range, 2 - 218) months. RESULTS Pts with late relapse were older - 35 years (23-57), whereas pts with early relapse - 30 years (16-63) (p=0.0008) and also had more frequent pure seminoma in primary tumor: 14/29 (48,3%) vs. 46/140 (32,8%), p=0.08. At the time of disease progression both groups were very similar according to well-known prognostic factors incl. IGCCCG classification. The only difference between groups was larger size of retroperitoneal lymph nodes in late (9 cm) than in early relapse (4 cm, p<0.0001). The outcome in pts with late relapse was significantly worse than in pts with early relapse: complete response rate after induction CT was 20.7% (6/29) vs. 42.1% (59/140) (p=0.01), three-year PFS - 70% vs. 84% (p=0.05, HR 2.1, 95%CI 1.0-7.6) and three-year OS - 72% vs. 88% (p=0.04, HR=2.4 95% CI 1.05-10.25), respectively. In pts with pure seminoma this difference in OS was even more significant: 65% vs. 91% (p=0.04, HR=3.8, 95%CI=1.06-32.4). CONCLUSIONS Late relapse following stage I GCT was associated with seminoma, older age and worse outcome after induction CT.