Saghatelyan Tatul, Tananyan Armen, Janoyan Naira, Tadevosyan Anna, Petrosyan Hasmik, Hovhannisyan Araxia, Hayrapetyan Lidia, Arustamyan Mikael, Arnhold Jürgen, Rotmann Andre-Robert, Hovhannisyan Areg, Panossian Alexander
National Center of Oncology, 76 Fanarjyan str, 0052 Yerevan, Armenia.
National Center of Oncology, 76 Fanarjyan str, 0052 Yerevan, Armenia.
Phytomedicine. 2020 Apr 18;70:153218. doi: 10.1016/j.phymed.2020.153218.
The clinical efficacy of curcumin has not yet been established for the treatment of cancer, despite a large body of evidence from numerous preclinical studies suggesting the therapeutic potential of curcumin, particularly in a synergistic combination with paclitaxel. The main obstacle in using curcumin for adjunctive cancer therapy is its low bioavailability via oral administration.
We assessed the efficacy and safety of intravenous curcumin infusion in combination with paclitaxel in patients with metastatic and advanced breast cancer.
A randomized, double-blind, placebo-controlled, parallel-group comparative clinical study was conducted.
A total of 150 women with advanced and metastatic breast cancer were randomly assigned to receive either paclitaxel (80 mg/m) plus placebo or paclitaxel plus curcumin (CUC-1®, 300 mg solution, once per week) intravenously for 12 weeks with 3 months of follow-up. The primary outcome was determined based on the objective response rate (ORR), as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). The secondary outcomes were progression-free survival (PFS), time to tumor progression (TTP), time to tumor treatment failure (TTTF), safety, and quality of life.
The intention-to-treat (ITT) analysis revealed that the ORR of curcumin was significantly higher than that of the placebo (51% vs. 33%, p < 0.01) at 4 weeks of follow-up. The difference between the groups was even greater when only patients who had completed the treatment (61% vs. 38%, odds ratio ==2.64, p < 0.01) were included. A superior effect of curcumin vs placebo was observed in both patients who had completed the treatment and all patients included in the ITT analysis, 3 months after termination of the treatment. No other significant differences were observed between the curcumin and the placebo groups, except for fatigue (3 vs. 10 patients, respectively; odds ratio ==3.7, p = 0.05). However, the patients' self-assessed overall physical performance was significantly higher with curcumin than the placebo during the treatment and at the end of the follow-up, suggesting better tolerance in the curcumin group.
Overall, treatment with curcumin in combination with paclitaxel was superior to the paclitaxel-placebo combination with respect to ORR and physical performance after 12 weeks of treatment. Intravenously administered curcumin caused no major safety issues and no reduction in quality of life, and it may be beneficial in reducing fatigue.
This is the first clinical study to explore the efficacy and safety of administering curcumin intravenously in combination with chemotherapy in the treatment of cancer patients.
尽管大量临床前研究证据表明姜黄素具有治疗潜力，尤其是与紫杉醇联合使用时具有协同作用，但姜黄素治疗癌症的临床疗效尚未确立。口服姜黄素用于辅助癌症治疗的主要障碍是其生物利用度低。
我们评估了静脉输注姜黄素联合紫杉醇治疗转移性和晚期乳腺癌患者的疗效和安全性。
进行了一项随机、双盲、安慰剂对照、平行组比较临床研究。
总共150例晚期和转移性乳腺癌女性患者被随机分配，分别接受静脉注射紫杉醇（80mg/m）加安慰剂或紫杉醇加姜黄素（CUC-1®，300mg溶液，每周一次）治疗12周，并随访3个月。主要结局根据实体瘤疗效评价标准（RECIST）评估的客观缓解率（ORR）确定。次要结局为无进展生存期（PFS）、肿瘤进展时间（TTP）、肿瘤治疗失败时间（TTTF）、安全性和生活质量。
意向性分析（ITT）显示，随访4周时，姜黄素组的ORR显著高于安慰剂组（51%对33%，p<0.01）。仅纳入完成治疗的患者时，两组之间的差异更大（61%对38%，优势比=2.64，p<0.01）。在完成治疗的患者以及ITT分析中纳入的所有患者中，治疗终止3个月后，均观察到姜黄素组相对于安慰剂组具有更好的疗效。除疲劳外（分别为3例对10例患者；优势比=3.7，p=0.05），姜黄素组和安慰剂组之间未观察到其他显著差异。然而，在治疗期间和随访结束时，患者自我评估的总体身体状况在姜黄素组显著高于安慰剂组，表明姜黄素组耐受性更好。
总体而言，治疗12周后，姜黄素联合紫杉醇治疗在ORR和身体状况方面优于紫杉醇-安慰剂联合治疗。静脉注射姜黄素未引起重大安全问题，也未降低生活质量，且可能有助于减轻疲劳。
这是第一项探索静脉注射姜黄素联合化疗治疗癌症患者的疗效和安全性的临床研究。
