Yogelzang N J, Herndon J E, Cirrincione C, Harmon D C, Antman K H, Corson J M, Suzuki Y, Citron M L, Green M R
Section of Hematolog/Oncology, University of Chicago Medical Center, Illinois 60637-1470, USA.
Cancer. 1997 Jun 1;79(11):2237-42. doi: 10.1002/(sici)1097-0142(19970601)79:11<2237::aid-cncr23>3.0.co;2-w.
Malignant mesothelioma is a disease that is refractory to chemotherapy. Therefore, the objective of this multi-institutional, cooperative group Phase II trial was to determine the efficacy of dihydro-5-azacytidine (DHAC), a pyrimidine analogue, in the treatment of malignant mesothelioma.
Forty-one patients with histologically confirmed malignant mesothelioma received 120-hour continuous infusions of DHAC (1,500 mg/m2/day every 21 days) until maximal response, intolerable toxicity, or disease progression.
One patient had a complete response, two had objective partial responses, and four had regression of evaluable disease. The overall response rate was 17%. The one complete responder remains without disease progression at 6 years. Chest pain and nausea were the most common toxicities. Supraventricular tachycardia and pericardial effusion occurred in 20% and 15% of patients, respectively. In most patients, gastrointestinal effects were manageable. There was no significant hematologic toxicity.
In malignant mesothelioma, a disease that is refractory to chemotherapy, dihydro-5-azacytidine has definite antitumor activity. Its modest hematologic toxicity profile favors its use in combination with other agents. Caution regarding cardiac arrhythmias and pericardial effusion is necessary.
恶性间皮瘤是一种对化疗难治的疾病。因此，这项多机构合作组II期试验的目的是确定嘧啶类似物二氢-5-氮杂胞苷（DHAC）治疗恶性间皮瘤的疗效。
41例经组织学确诊的恶性间皮瘤患者接受DHAC持续120小时输注（每21天1500mg/m²/天），直至出现最大反应、不可耐受的毒性或疾病进展。
1例患者完全缓解，2例客观部分缓解，4例可评估疾病出现消退。总缓解率为17%。唯一的完全缓解者在6年时无疾病进展。胸痛和恶心是最常见的毒性反应。室上性心动过速和心包积液分别发生在20%和15%的患者中。在大多数患者中，胃肠道反应可控。无明显血液学毒性。
在对化疗难治的恶性间皮瘤中，二氢-5-氮杂胞苷具有明确的抗肿瘤活性。其适度的血液学毒性特征有利于与其他药物联合使用。必须注意心律失常和心包积液问题。
