PHASE-II TRIALS WITH FLAVONE ACETIC-ACID (NCS-347512, LM975) IN PATIENTS WITH ADVANCED-CARCINOMA OF THE BREAST, COLON, HEAD AND NECK AND MELANOMA
PHASE-II TRIALS WITH FLAVONE ACETIC-ACID (NCS-347512, LM975) IN PATIENTS WITH ADVANCED-CARCINOMA OF THE BREAST, COLON, HEAD AND NECK AND MELANOMA
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DOI：
10.1007/bf00171993
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发表时间：
1990-01-01
影响因子：
3.4
通讯作者：
CAVALLI, F
中科院分区：
文献类型：
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作者：
KAYE, SB;CLAVEL, M;CAVALLI, F
黄酮乙酸的II期试验已在总共87名患者中进行，包括17名晚期乳腺癌患者、23名晚期结直肠癌患者、25名晚期恶性黑色素瘤患者和22名晚期头颈癌患者。结直肠癌和黑色素瘤患者既往未接受过化疗;乳腺癌和头颈癌患者既往接受过化疗，中位数分别为5种和2种药物。使用的方案为每周一次方案，剂量为4.8 gms/m2，输注1小时，在FAA之前和之后给予碱化（静脉注射碳酸氢钠）。在每周6次给药后进行重新评估，尽管23例患者的给药少于6次，因为15例患者的早期疾病进展，5例患者的过度毒性。另外3例患者在接受FAA后72小时内死亡，尽管每例病例的确切死因尚未确定，但不能排除FAA毒性。治疗通常是可控的，毒性的主要表现包括不适的发热和潮红、恶心、腹泻和视力顺应性。8例患者还记录了低血压。尽管在3例乳腺癌患者、1例晚期结直肠癌患者、2例晚期黑色素瘤患者和4例头颈癌患者中观察到疾病稳定，但在任何患者亚组中均未观察到客观缓解。进一步的II期研究，使用更高的剂量8.6 gm/m2，每周一次，持续6小时，目前正在欧洲进行。然而，迄今为止的II期研究表明，FAA作为单药每周以最大耐受剂量在1小时内给药具有抗肿瘤活性。
Phase II trials of flavone acetic acid have been performed in a total of 87 patients including 17 with advanced breast cancer, 23 with advanced colorectal cancer, 25 with advanced malignant melanoma and 22 with advanced head and neck cancer. Patients with colorectal cancer and melanoma had received no prior chemotherapy; in breast and head and neck cancer patients prior chemotherapy had been given with a median of 5 and 2 drugs respectively. The schedule used was a once-weekly regime, with a dose of 4.8 gms/m2 given as a 1 hour infusion, together with alkalinization (with i.v. sodium bicarbonate) given before and after FAA. Reassessment was performed after 6 weekly doses, although in 23 patients fewer than 6 doses were given, because of early disease progression in 15, and undue toxicity in 5. An additional 3 patients died within 72 hours of having received FAA and, although the precise cause of death in each case was no established, FAA toxicity could not be excluded. Treatment was generally manageable, the major manifestations of toxicity comprising uncomfortable warmth and flushes, nausea, diarrhoea, and visual compliants. Hypotension was also documented in 8 patients. No objective responses were seen in any of the patient sub-groups, although disease-stabilization was seen in 3 patients with breast cancer, 1 patient with advanced colorectal cancer, 2 patients with advanced melanoma and 4 patients with head and neck cancer. Further Phase II studies, using a higher dose of 8.6 gm/m2 over 6 hours once weekly, are currently in progress in Europe. However, Phase II studies to date indicate to antitumor activity of FAA given weekly as a single agent at the maximally tolerated dose over 1 hour.