Morabito Alessandro, Daniele Gennaro, Costanzo Raffaele, Favaretto Adolfo Gino, Filipazzi Virgilio, Rossi Antonio, Gebbia Vittorio, Castiglione Federico, Cavanna Luigi, Maiello Evaristo, Sandomenico Claudia, Bonanno Laura, Piazza Elena, Maione Paolo, Piccirillo Maria Carmela, Di Maio Massimo, Rocco Gaetano, Gallo Ciro, Perrone Francesco, Gridelli Cesare
Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy.
Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy.
Lung Cancer. 2017 Jun;108:15-21. doi: 10.1016/j.lungcan.2017.02.016. Epub 2017 Feb 27.
Data supporting the prognostic role of chemotherapy induced haematological toxicity suggest that toxicity-adjusted-dosing (TAD) of chemotherapy might improve treatment efficacy. We tested whether TAD of the cisplatin-etoposide combination might improve the response rate, in previously untreated extensive stage disease (ED)-SCLC patients, as compared with standard fixed-dosing (FD).
Patients with ED-SCLC were randomized to receive either TAD or FD of cisplatin-etoposide as first-line treatment. Primary endpoint was the objective response rate (ORR) according to the RECIST 1.0 criteria, secondary endpoints included progression free survival (PFS), overall survival (OS) and toxicity.
Hundred-fifty-eight patients were randomized. Most patients were male, with ECOG-PS 1, without brain metastases and had not received radiotherapy before study entry. Response rate was 54.4 (95%CI: 43.5-64.9%) and 58.2 (95%CI: 47.2-68.5%) in the control and experimental arms, respectively (P=0.75). No significant differences were found in terms of PFS (HR 1.04; 95%CI: 0.74-1.44, P=0.84) and OS (HR1.01; 95%CI 0.71-1.42, p=0.97). Seven patients died on treatment, one in the standard arm and 6 in the experimental arm. The most frequent cause of death was neutropenia with infection and, apart in one, death was not related to dose modification. Severe toxicity was more frequent in the experimental arm (91% vs 60%).
In our population of chemonaïve ED SCLC patients, TAD failed to improve the ORR, PFS and OS over the FD of cisplatin-etoposide as first line chemotherapy and was associated with increased toxicity.
支持化疗所致血液学毒性预后作用的数据表明，化疗的毒性调整剂量（TAD）可能会提高治疗效果。我们测试了顺铂-依托泊苷联合方案的TAD与标准固定剂量（FD）相比，是否能提高初治广泛期疾病（ED）-小细胞肺癌（SCLC）患者的缓解率。
将ED-SCLC患者随机分为接受顺铂-依托泊苷的TAD或FD作为一线治疗。主要终点是根据RECIST 1.0标准的客观缓解率（ORR），次要终点包括无进展生存期（PFS）、总生存期（OS）和毒性。
158例患者被随机分组。大多数患者为男性，ECOG-PS为1，无脑转移，且在研究入组前未接受过放疗。对照组和试验组的缓解率分别为54.4（95%CI：43.5-64.9%）和58.2（95%CI：47.2-68.5%）（P=0.75）。在PFS（HR 1.04；95%CI：0.74-1.44，P=0.84）和OS（HR1.01；95%CI 0.71-1.42，p=0.97）方面未发现显著差异。7例患者在治疗期间死亡，标准组1例，试验组6例。最常见的死亡原因是中性粒细胞减少伴感染，除1例死亡外，其余死亡均与剂量调整无关。试验组严重毒性更常见（91%对60%）。
在我们的初治ED SCLC患者群体中，与顺铂-依托泊苷的FD作为一线化疗相比，TAD未能提高ORR、PFS和OS，且与毒性增加相关。
