Initial Chemotherapy Choice

Chemotherapy is basic treatment of SCLC, always used, even for the rare surgically treated patients, according to a neoadjuvant or an adjuvant mode. For all other inoperable patients, it is an emergency to begin it as soon as possible, the day of histologic diagnosis. It cannot be the same for all patients like yet often recommended for cisplatin-etoposide as a standard [1]. This statement has never been demonstrated! Patients with good clinical prognosis factors must receive a four-drug protocol treatment. A phase III randomised trial had already proved survival benefit of epidoxorubicin plus cyclophosphamide addition to cisplatin-etoposide compared to cisplatin-etoposide alone in selected extensive SCLC [2]. This result is not contradictory with our results obtaining no survival difference between cyclophosphamide-doxorubicin-etoposide (CDE) and the same plus cisplatin (PCDE) for 457 patients with poor prognosis data [3], because the choice of drugs has to be adapted to the patient status. For extensive SCLC, no progress has recently been identified, as concluded in a 2008 editorial analysing interest of irinotecan and carboplatin association [4]; we presently prefer to keep our old CDE, effective and less toxic (in absence of cardiac contra-indication).

At the opposite, for limited forms patients with good prognosis factors research of optimal dosage for first course is very important. We demonstrated in a 1280 patients multivariate analysis of pretherapeutic and therapeutic prognosis factors that complete response after the second treatment session was firstly predictive of longer survival (p<0.0001), more powerful than performance status or initial extension [5]. Value of early response is so sustained by a forgotten fifteen-years trial, never reproduced but well proving that single increase of 25% cisplatin and cyclophophamide dosages at the first course of a PCDE regimen obtained a 2-year accrual survival from 26% to 43%, comparing to a PCDE without dosage increase at the first course [6]. Surely, it is more easy to associate cisplatin-etoposide to a concurrent thoracic radiotherapy limiting irradiation toxicity, but this standard treatment is not optimal for limited forms patients with good performance status. These ones can receive a dose-dense chemotherapy supported by G-CSF, without exceeding haematological toxicity limits.

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