Tsuchiya H, Tomita K, Yamamoto N, Mori Y, Asada N
Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan.
Anticancer Res. 1998 Sep-Oct;18(5B):3651-6.
We report here the results of preoperative and postoperative caffeine-potentiated chemotherapy and limb-sparing surgery for soft-tissue sarcomas. Thirty-six patients with histologically high-grade soft-tissue sarcomas were treated with caffeine-potentiated chemotherapy and conservative surgery (25 cases of limb-sparing surgery and 11 of local tumor excision). There were 13 patients with malignant fibrous histiocytoma (MFH), eight with synovial sarcoma, five with liposarcoma, four with malignant schwannoma, four with epithelioid sarcoma, one with leiomyosarcoma and one with extraskeletal chondrosarcoma. Nine patients were at stage III with lung metastasis and the other 27 at stage IIB without metastasis; 22 were male and 14 female with a mean age of 48 years, ranging from 16 to 77. For intra-arterial preoperative chemotherapy, we administered 2-5 courses of cisplatin (120 mg/m2), doxorubicin (30 mg/m2 x 2 days), and caffeine (1.5 g/m2 x 3 days) to 18 patients, and cisplatin and caffeine to the other 18. Although 15 patients had already undergone unplanned tumor excision at other hospitals before preoperative chemotherapy, all patients underwent definitive limb-sparing surgery after the preoperative chemotherapy. Surgical margins were wide for 28 patients, marginal for three and intralesional for five. Local tumor recurrence was seen in one patient with MFH and one with epithelioid sarcoma. Of the 27 stage IIB patients, lung metastasis newly developed in one with MFH, three with synovial sarcoma, two with malignant schwannoma and one with leiomyosarcoma. As for the effects of preoperative chemotherapy in the 33 eligible cases, radiographically confirmed complete response was seen in two patients, partial response in 20 and no response in 11. Histological response to this preoperative chemotherapy consisted of grade I (no response) in 14, grade II (50-90% necrosis) in four, grade III (> 90% necrosis) in eight, and grade IV (no viable cells) in seven cases. An overall objective response rate of 73% was obtained. With the mean follow-up period of 58 months (5-101 months), the overall 5-year cumulative survival rate ascertained with the Kaplan-Meier method was 63% and that of stage II patients 81%. Eight of the nine stage III patients died of metastatic disease within two and a half years from the beginning of the treatment. In conclusion, caffeine-potentiated chemotherapy and limb-sparing surgery brought good results for stage II nonmetastatic soft-tissue sarcomas. The problem of treatment for stage III metastatic soft-tissue sarcomas, however, remains unsolved.
我们在此报告软组织肉瘤术前及术后咖啡因增强化疗与保肢手术的结果。36例组织学上高级别软组织肉瘤患者接受了咖啡因增强化疗及保守手术（25例行保肢手术，11例行局部肿瘤切除）。其中有13例恶性纤维组织细胞瘤（MFH）患者、8例滑膜肉瘤患者、5例脂肪肉瘤患者、4例恶性神经鞘瘤患者、4例上皮样肉瘤患者、1例平滑肌肉瘤患者和1例骨外软骨肉瘤患者。9例患者处于III期伴肺转移，另外27例处于IIB期无转移；男性22例，女性14例，平均年龄48岁，范围为16至77岁。对于动脉内术前化疗，我们对18例患者给予2 - 5个疗程的顺铂（120 mg/m²）、阿霉素（30 mg/m²×2天）和咖啡因（1.5 g/m²×3天），对另外18例患者给予顺铂和咖啡因。尽管15例患者在术前化疗前已在其他医院接受了意外的肿瘤切除，但所有患者在术前化疗后均接受了确定性保肢手术。28例患者手术切缘为广泛切除，3例为边缘切除，5例为病灶内切除。1例MFH患者和1例上皮样肉瘤患者出现局部肿瘤复发。在27例IIB期患者中，1例MFH患者、3例滑膜肉瘤患者、2例恶性神经鞘瘤患者和1例平滑肌肉瘤患者新出现肺转移。至于33例符合条件病例的术前化疗效果，影像学证实完全缓解的有2例，部分缓解的有20例，无缓解的有11例。术前化疗的组织学反应包括14例I级（无反应）、4例II级（50 - 90%坏死）、8例III级（> 90%坏死）和7例IV级（无存活细胞）。总体客观缓解率为73%。平均随访期为58个月（5 - 101个月），采用Kaplan - Meier法确定的总体5年累积生存率为63%，II期患者为81%。9例III期患者中有8例在治疗开始后两年半内死于转移性疾病。总之，咖啡因增强化疗与保肢手术对II期非转移性软组织肉瘤取得了良好效果。然而，III期转移性软组织肉瘤的治疗问题仍未解决。
