R. Neuhauss

Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin/Etoposide/ Vincristine Therapy in Small Cell Lung Cancer

Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC; 14% complete response, CR; and 61% CR + partial response, PR). The combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease, with 52% CR. The median survival time with this combination was 13 months in patients with limited disease and 9.5 months in those with extensive disease. The 4-year survival rates are 26% in limited disease and 8% in extensive disease, with a plateau of the survival curve. This regimen is highly effective and exhibits low toxicity in SCLC. To evaluate the role of carboplatin in combination chemotherapy in patients with extensive SCLC, a phase III trial was performed. In this ongoing trial comparing CEV and etoposide/vincristine in SCLC patients with extensive disease, CR and overall response rates are higher in the CEV arm (CR 32 vs. 17%, CR + PR 80 vs. 60%), with statistically significant difference. In summary, chemotherapy regimens containing platinum compounds are among the most active in the treatment of SCLC. The use of the new compound carboplatin instead of cisplatin has led to similar or increased remission rates and is preferable because it has fewer side effects. Preliminary results from this ongoing, prospective, randomized phase III trial will be presented.