Elias A D, Ayash L, Frei E, Skarin A T, Hunt M, Wheeler C, Schwartz G, Mazanet R, Tepler I, Eder J P
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA 02115.
J Natl Cancer Inst. 1993 Apr 7;85(7):559-66. doi: 10.1093/jnci/85.7.559.
Conventional-dose chemotherapy for small-cell lung cancer has resulted in high response rates but rarely in a cure. The addition of thoracic radiotherapy (chemoradiotherapy) has improved survival for patients having limited disease, resulting in a median survival of 14-18 months. Previous trials evaluating high-dose chemotherapy and autologous bone marrow transplantation have demonstrated enhanced complete response rates without documenting overall survival benefit.
The purpose of this phase II trial was to determine the disease-free and overall survival, toxic effects, and relapse patterns in patients with limited small-cell lung cancer who were in partial or complete response to first-line conventional-dose chemotherapy and then received intensive systemic combined modality therapy.
Adults with stage III small-cell lung cancer who had achieved at least a partial response to conventional-dose induction chemotherapy were treated with high-dose cyclophosphamide, cisplatin, and carmustine combined with autologous bone marrow transplantation. Cumulative doses of the three drugs were 5625, 165, and 480 mg/m2, respectively. After recovery, patients received thoracic radiotherapy (50-60 Gy in 25-30 fractions over 5-6 weeks) and cranial radiotherapy (30 Gy in 15 fractions during 3 weeks).
Of 19 patients in the study, six had achieved complete response, eight had a greater than 90% reduction in tumor size, and five had a 50%-90% reduction in tumor size. After high-dose therapy, 15 of the 19 were in complete response. Overall, median time to treatment failure after high-dose therapy was 12 months. Overall survival was 73% (95% confidence interval [CI] = 42%-89%) at 1 year and 53% (95% CI = 22%-77%) at 2 years. Of the 14 patients in or near complete response before high-dose therapy, 10 remain disease free with no further chemotherapy a median of 15 (4-69+) months after therapy. Actuarial 2-year disease-free survival is 57% (95% CI = 20%-82%). One patient died of Candida sepsis. Morbidity was low, and most patients returned to full-time work. With the exception of herpes zoster, there were no complications more than 3 months after high-dose therapy.
The majority of the patients in this study are experiencing prolonged and unmaintained disease-free survival. Our findings suggest that patients in or near complete response before high-dose therapy have the most favorable prognosis.
A randomized comparison between this approach and conventional-dose therapy is planned to define the utility of dose intensification with autologous bone marrow transplantation in the treatment of patients with limited-stage small-cell lung cancer who are in or near complete response.
小细胞肺癌的传统剂量化疗已产生较高的缓解率，但很少能治愈。添加胸部放疗（放化疗）可改善疾病局限患者的生存率，中位生存期为14 - 18个月。既往评估高剂量化疗和自体骨髓移植的试验已证明完全缓解率有所提高，但未记录总体生存获益。
本II期试验的目的是确定对一线传统剂量化疗有部分或完全缓解的局限期小细胞肺癌患者接受强化全身联合治疗后的无病生存期和总生存期、毒性作用及复发模式。
对传统剂量诱导化疗至少有部分缓解的III期小细胞肺癌成人患者，采用高剂量环磷酰胺、顺铂和卡莫司汀联合自体骨髓移植进行治疗。三种药物的累积剂量分别为5625、165和480 mg/m²。恢复后，患者接受胸部放疗（5 - 6周内分25 - 30次给予50 - 60 Gy）和颅脑放疗（3周内分15次给予30 Gy）。
研究中的19例患者中，6例达到完全缓解，8例肿瘤大小缩小超过90%，5例肿瘤大小缩小50% - 90%。高剂量治疗后，19例中有15例达到完全缓解。总体而言，高剂量治疗后至治疗失败的中位时间为12个月。1年时总生存率为73%（95%置信区间[CI]=42% - 89%），2年时为53%（95% CI = 22% - 77%）。在高剂量治疗前处于完全缓解或接近完全缓解的14例患者中，10例在治疗后中位15（4 - 69 +）个月无病，无需进一步化疗。2年无病生存率的精算值为57%（95% CI = 20% - 82%）。1例患者死于念珠菌败血症。发病率较低，大多数患者恢复全职工作。除带状疱疹外，高剂量治疗3个月后无其他并发症。
本研究中的大多数患者经历了延长的、无需维持治疗的无病生存期。我们的研究结果表明，高剂量治疗前处于完全缓解或接近完全缓解的患者预后最有利。
计划对该方法与传统剂量治疗进行随机比较，以确定自体骨髓移植强化剂量在治疗处于完全缓解或接近完全缓解的局限期小细胞肺癌患者中的效用。
