Jean-Marc Classe, Pierre Meeus, Delphine Hudry, Romuald Wernert, François Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Fabrice Lecuru, Gwenaël Ferron, Cécile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Marc Pocard, Constantin Georgeac, Sébastien Gouy, Olivier Glehen
{"title":"复发性卵巢癌腹腔内热化疗（CHIPOR）：随机、开放标签、3 期试验","authors":"Jean-Marc Classe, Pierre Meeus, Delphine Hudry, Romuald Wernert, François Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Fabrice Lecuru, Gwenaël Ferron, Cécile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Marc Pocard, Constantin Georgeac, Sébastien Gouy, Olivier Glehen","doi":"10.1016/s1470-2045(24)00531-x","DOIUrl":null,"url":null,"abstract":"<h3>Background</h3>Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.<h3>Methods</h3>The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m<sup>2</sup> in 2 L/m<sup>2</sup> of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT01376752</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] <em>vs</em> 30 [14%]), hepatotoxicity (23 [11%] <em>vs</em> 18 [9%]), electrolyte disturbance (28 [14%] <em>vs</em> two [1%]), and renal failure (20 [10%] <em>vs</em> three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.<h3>Interpretation</h3>Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival.<h3>Funding</h3>French National Cancer Institute and French League Against Cancer.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"158 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial\",\"authors\":\"Jean-Marc Classe, Pierre Meeus, Delphine Hudry, Romuald Wernert, François Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Fabrice Lecuru, Gwenaël Ferron, Cécile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Marc Pocard, Constantin Georgeac, Sébastien Gouy, Olivier Glehen\",\"doi\":\"10.1016/s1470-2045(24)00531-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Background</h3>Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.<h3>Methods</h3>The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m<sup>2</sup> in 2 L/m<sup>2</sup> of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\\\"Opens in new window\\\" focusable=\\\"false\\\" height=\\\"20\\\" viewbox=\\\"0 0 8 8\\\"><path d=\\\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\\\"></path></svg></span>, <span><span>NCT01376752</span><svg aria-label=\\\"Opens in new window\\\" focusable=\\\"false\\\" height=\\\"20\\\" viewbox=\\\"0 0 8 8\\\"><path d=\\\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\\\"></path></svg></span>.<h3>Findings</h3>Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] <em>vs</em> 30 [14%]), hepatotoxicity (23 [11%] <em>vs</em> 18 [9%]), electrolyte disturbance (28 [14%] <em>vs</em> two [1%]), and renal failure (20 [10%] <em>vs</em> three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.<h3>Interpretation</h3>Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. 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引用次数: 0
摘要
背景卵巢癌细胞减灭术间隔期腹腔内热化疗（HIPEC）可提高总生存率，但其对复发疾病的作用尚不确定。我们的目的是比较复发性卵巢癌手术期间接受或不接受 HIPEC 治疗的患者的疗效。方法 多中心、开放标签、随机、3 期 CHIPOR 试验在法国、比利时、西班牙和加拿大的 31 个地点进行，入选者为完成铂类化疗至少 6 个月后首次复发的上皮性卵巢癌患者。符合条件的患者年龄在 18 岁或以上，WHO 体征表现小于 2 级。在进行了六个周期的铂类化疗（可选择贝伐单抗）后，可进行完全细胞减灭术的患者在手术过程中通过网络系统和最小化程序，按1:1的比例被随机分配接受或不接受HIPEC治疗（顺铂75毫克/平方米，溶于2升/平方米的血清中，温度为41±1°C，时间为60分钟），分层因素包括中心、细胞减灭术评分完成度、无铂间隔时间，以及后来计划使用的多（ADP-核糖）聚合酶抑制剂。主要终点是总生存期，对所有随机分配的患者进行意向治疗分析。2011年5月11日至2021年5月14日期间，415名女性患者被随机分配（207人接受HIPEC治疗，208人未接受HIPEC治疗）。在主要分析中（中位数随访 6-2 年，IQR 4-1-8-1），有 268 名（65%）患者死亡（HIPEC 组 207 人中有 126 人[61%]死亡；无 HIPEC 组 208 人中有 142 人[68%]死亡）。HIPEC可明显提高总生存率（分层危险比为0-73，95% CI为0-56-0-96；P=0-024）。采用HIPEC治疗的中位总生存期为54-3个月（95% CI 41-9-61-7），而不采用HIPEC治疗的中位总生存期为45-8个月（38-9-54-2）。术后60天内，接受HIPEC治疗的207例患者中有102例（49%）发生了3级或更严重的不良事件，而未接受HIPEC治疗的208例患者中有56例（27%）发生了3级或更严重的不良事件，最常见的不良事件是贫血（47例[23%] vs 30例[14%]）、肝毒性（23例[11%] vs 18例[9%]）、电解质紊乱（28例[14%] vs 2例[1%]）和肾功能衰竭（20例[10%] vs 3例[1%]）。首次上皮性卵巢癌复发时，对铂类化疗有反应后，在细胞剥脱手术中加入 HIPEC 可显著提高总生存率。在治疗晚期首次复发的高分化浆液性或高分化子宫内膜样卵巢癌患者时，如果患者可以在专科中心接受完全的细胞减灭术，则应考虑使用铂类HIPEC来延长患者的总生存期。
Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial
Background
Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.
Methods
The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m2 in 2 L/m2 of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752.
Findings
Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.
Interpretation
Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival.
Funding
French National Cancer Institute and French League Against Cancer.
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