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A Multicenter Randomized Phase III Study Comparing Paclitaxel-Cisplatin-Etoposide (TEP) Versus Cisplatin-Etoposide (EP) as Front - Line Treatment in Patients with Small Cell Lung Cancer (SCLC)

Diana Stripp, MD
OncoLink Assistant Editor
Last Modified: May 22, 2000

Presenter: Dimitrios Mavroudis
Affiliation: The Greek Lung Cancer Cooperative Group

Background:
The combination of etoposide (E) and cisplatin (P) is standard first line treatment for small cell lung cancer (SLSC). A complete response (CR) rate of 30-40% is seen in limited stage (LS) and 10-20% in extensive stage (ES). Paclitaxel (T) is an active agent in SCLC with 34 % partial response rate (J Clin Oncol 1995 13:1430). Previous Phase I (Semin Oncol 1997 Aug; 24 (4 Suppl 12): S12-144-S12-148) and Phase II (J Clin Oncol 1999 17: 2309) studies have shown that the combination of Paclitaxel-Cisplatin-Etoposide (TEP) was active in SCLC. This multicenter Phase III trial was designed to compare the activity and toxicity of TEP versus EP in untreated patients with SCLC.

Materials and Methods:

• Eligibility: Pts with a histologically confirmed SCLC, age between 18-78, performance status 0-2, no previous treatment, if CNS metastasis present ? either stable or s/p radiation (XRT) and with a life expectancy ³ 3 mos.

• Cycles were repeated every 28 days.

• Responding limited stage (LS) pts proceed to thoracic XRT after completion of chemotherapy and then prophylactic cranial irradiation (PCI)

• The study was stopped prematurely due to excessive toxicity of TEP regimen.

• 133 chemotherapy-naïve SCLC patients were randomized to receive either:

• TEP - T 175 mg/m2 IV-3hrs D-1, E 80mg/m2/d IV D2-4, P 80mg/m2 IV D2, plus prophylactic G-CSF 5 mcg/kg/d SC D5-15 for all patients, or

• EP - E 120mg/m2/d IV D1-3, P 80mg/m2 IV D1, with G-CSF only for pts developing severe neutropenia.

• 62 pts received TEP and 71 EP with 49/62 and 69/71 evaluable for response/toxicity respectively.

• Limited Stage (LS) was present in 29/62 (47%) pts on TEP and 30/71 (41%) on EP.

• Responses CR +PR: 3(5%) + 28(45%) for TEP and 3 (4%) + 30(42%) for EP (p=0.7).

• Duration of response, median survival and 1-yr survival were 7 and 10.5 mos and 43% for TEP vs. 6 and 11.5 mos and 45% for EP (p=NS).

• In the subgroup analysis, TEP was more active than EP in pts with extensive disease (p=0.03) but without any survival benefit.

• A total of 547 cycles of treatment have been administered (241 TEP/306 EP) with a median of 4 and 5 cycles/pts respectively.

• Toxicity (WHO) was (TEP/EP): Grade 3 neutropenia 44%/39%, grade 3 thrombocytopenia 18%/6% (p+0.02), grade 3 diarrhea 8%/0 (p=0.01), grade 3 neurotoxicity 8%/1.4% (p=0.06), grade 3 asthenia 11%/3% (p=0.05), Febrile neutropenia 6%/3%.

• There were 8 toxic deaths (4 neutropenic sepsis, 1 grade 4 diarrhea, 1 CVA, 1 pneumonia and 1 sudden death) with TEP vs none with EP.

• TEP and EP regimens have comparable activity as first line treatment in SCLC.

• TEP is significantly more toxic than EP

• Though TEP has similar activity as EP in SCLC and shows more activity in the LS SCLC, but due to its toxicity, EP remains the standard treatment in SCLC due to its better toxicity profile.