近日，英国伦敦大学学院Mary McCormack团队研究了诱导化疗联合标准放化疗治疗晚期宫颈癌的疗效。这一研究成果发表在2024年10月14日出版的《柳叶刀》杂志上。

局部晚期宫颈癌需接受放化疗（标准治疗），但许多患者仍会复发并死于转移性疾病。课题组研究了加或不加诱导化疗的放化疗，以确定诱导化疗是否能提高无进展生存率和总生存率。

研究组在巴西、印度、意大利、墨西哥和英国的32个医疗中心进行了一项多中心随机3期试验。患有局部晚期宫颈癌（FIGO 2008 IB1期淋巴结受累疾病，或IB2、IIA、IIB、IIIB或IVA期疾病）的成人（年龄≥18岁）被随机分配（1:1），使用中央电子系统，通过最小化，接受标准的基于顺铂的化学放射治疗（每周一次静脉注射顺铂40 mg/m²，为期5周，45.0–50.4 Gy的外束放射治疗，分20–28个部分进行，加上近距离放射治疗，以实现最低2 Gy当量剂量78–86 Gy）或诱导化疗（接受者操作曲线面积2下每周一次静脉注射卡铂，紫杉醇80 mg/m²，持续6周），然后进行标准的基于顺铂的放化疗。分层因素包括招募部位、分期、淋巴结状态、三维适形放疗或调强放疗、年龄、肿瘤大小和组织学（鳞状细胞与非鳞状细胞）。主要终点是意向治疗人群的无进展生存期和总生存期。

2012年11月8日至2022年11月17日，500名符合条件的患者被纳入研究，并随机分配到单纯放化疗组（n=250）或诱导化疗加放化疗组。在500名患者中，354名（70%）患有IIB期疾病，56名（11%）患有IIIB期疾病。215名患者（43%）的盆腔淋巴结呈阳性。230名（92%）接受诱导化疗的患者至少有五个周期。诱导化疗和放化疗之间的中位间隔为7天。诱导化疗加放化疗组212名（85%）参与者和单独放化疗组224名（90%）参与者接受了四个或更多周期的顺铂治疗。462名（92%）参与者接受了外照射放疗和近距离放疗，中位总治疗时间为45天。中位随访67个月后，诱导化疗加放化疗组的5年无进展生存率为72%，单纯放化疗组为64%，风险比（HR）为0.65（95%CI 0.46-0.91，p=0.013）。诱导化疗加放化疗组5年总生存率为80%，单纯放化疗组为72%，HR为0.60（95%CI 0.40-0.91，p=0.015）。诱导化疗加放化疗组250人中有147人（59%）报告了3级或以上不良事件，而单独放化疗组的250人中只有120人（48%）报告了这些不良事件。

研究结果表明，短期诱导化疗加放化疗可显著提高局部晚期宫颈癌患者的生存率。

附：英文原文

Title: Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial

Author: Mary McCormack, Gemma Eminowicz, Dolores Gallardo, Patricia Diez, Laura Farrelly, Christopher Kent, Emma Hudson, Miguel Panades, Tony Mathew, Anjana Anand, Mojca Persic, Jennifer Forrest, Rajanee Bhana, Nicholas Reed, Anne Drake, Madhavi Adusumalli, Asima Mukhopadhyay, Margaret King, Karen Whitmarsh, John McGrane, Nicoletta Colombo, Choi Mak, Ranajit Mandal, Rahul Roy Chowdhury, Gabriela Alamilla-Garcia, Adriana Chávez-Blanco, Hilary Stobart, Amanda Feeney, Simran Vaja, Anne-Marie Hacker, Allan Hackshaw, Jonathan Andrew Ledermann, Nicholas Reed, Anne Drake, Faheem Bashir, Audrey Cook, Ranajit Mandal, Lisa Barraclough, Sidarth Dubey, Won-Ho Edward Park, Maria Pilar, Dolores Gallardo, Gabriela Alamilla-Garcia, Nicoletta Colombo, Madhavi Adusumalli, Christopher Kent, Miguel Panades, Margaret King, Robert Wade, Jennifer Forrest, Choi Mak, Anjana Anand, John McGrane, Mojca Persic, Jennifer Forrest, Rajanee Bhana, Kate Lankester, Rahul Roy Chowdhury, Vicky McFarlane, Melanie Powell, Karen Whitmarsh, Mary McCormack, Gemma Eminowicz, Emma Hudson, Tony Mathew

Issue&Volume: 2024-10-14

Abstract:

Background

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

Methods

The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0–50·4 Gy external beam radiotherapy delivered in 20–28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78–86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35.

Findings

Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46–0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40–0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group.

Interpretation

Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.

DOI: 10.1016/S0140-6736(24)01438-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01438-7/abstract