Nemours Children's Specialty Care and Wolfson Children's Hospital, Jacksonville, Florida.
University of California at Davis Comprehensive Cancer Center, Sacramento, California.
Cancer. 2022 Mar 1;128(5):1057-1065. doi: 10.1002/cncr.34014. Epub 2021 Nov 11.
The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease.
In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility.
One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively.
The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.
儿童肿瘤学组（COG）采用顺铂、5-氟尿嘧啶和长春新碱（C5V）作为标准疗法，此前 INT-0098 研究表明，与顺铂和阿霉素相比，该疗法在统计学上具有等效的生存率，但毒性更小。随后的经验表明，阿霉素对 C5V 后复发疾病的患者有效，这表明它可以被纳入强化治疗方案，以治疗晚期疾病患者。
在这项非随机、3 期 COG 试验中，主要目的是探索在考虑为中危患者时，在 C5V 中加入阿霉素的新型治疗性顺铂、5-氟尿嘧啶、长春新碱和阿霉素（C5VD）方案的可行性和毒性。符合条件的患者为不可切除的非转移性疾病。在诊断时完全切除且局部病理显示小细胞未分化组织学的患者，也有资格评估可行性。
2009 年 9 月 14 日至 2012 年 3 月 12 日期间，共有 102 例可评估患者入组。C5VD 的给药是可行且可耐受的：顺铂、5-氟尿嘧啶、阿霉素和长春新碱的目标剂量的平均百分比分别为 96%（95%CI，94%-97%）、96%（95%CI，94%-97%）、95%（95%CI，93%-97%）和 90%（95%CI，87%-93%）。毒性在预期范围内，1 例患者首次出现死亡事件。最常见的不良事件是发热性中性粒细胞减少症（n=55[54%]）、感染（n=48[47%]）、黏膜炎（n=31[30%]）、低钾血症（n=39[38%]）和天门冬氨酸氨基转移酶升高（n=28[27%]）。93 例未完全切除诊断疾病的患者的 5 年无事件生存率和总生存率分别为 88%（95%CI，79%-93%）和 95%（95%CI，87%-98%）。
在 C5V 的先前标准方案中加入阿霉素是可行、耐受和有效的，这表明 C5VD 是未来临床试验的一个不错的方案。
