CHEMOTHERAPY
RETINOL CHEMO-PREVENTION. Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. The aim of the study was to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene or retinol. Subjects were randomly assigned to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed-up through death and cancer registries over 5 years. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomized to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomized to beta-carotene. Mesothelioma was the most common single cause of death in the study. The relative rate of mesothelioma for those on retinol compared with those on beta-carotene was 0.24. There was a higher rate of ischaemic heart disease mortality in the retinol group. The results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation. "Vitamin A and cancer prevention II: a comparison of the effects of retinol and beta-carotene", de Klerk, et al., International Journal of Cancer, 75(3):362-7, January 30, 1998.
Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. The aim of the study was to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene or retinol. Subjects were randomly assigned to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed-up through death and cancer registries over 5 years. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomized to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomized to beta-carotene. Mesothelioma was the most common single cause of death in the study. The relative rate of mesothelioma for those on retinol compared with those on beta-carotene was 0.24. There was a higher rate of ischaemic heart disease mortality in the retinol group. The results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation. "Vitamin A and cancer prevention II: a comparison of the effects of retinol and beta-carotene", de Klerk, et al., International Journal of Cancer, 75(3):362-7, January 30, 1998.
GOOD SYMPTOM RELIEF WITH MVP CHEMOTHERAPY. Over the course of more than 10 years, 39 patients with advanced inoperable malignant mesothelioma were treated with palliative mitomycin-C, vinblastine and cisplatin (MVP) chemotherapy. Eight of 39 patients (20%) achieved an objective partial response with a median duration of nine months; only five patients had progression of disease during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their symptomology with particularly good responses for pain. These benefits were independent of performance status. Resolution of symptoms was achieved in all responding patients within two treatment cycles. The treatment was well tolerated with only four patients developing grade 3 leukopenia (white blood cell reduction) and three with grade 3 nausea. MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic relief. These results should be the basis for further trials of MVP in the management of malignant mesothelioma with symptom control as a principal endpoint. "Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in malignant mesothelioma", Middleton, et al., Annals of Oncology, 9(3):269-73, March 1998. Over the course of more than 10 years, 39 patients with advanced inoperable malignant mesothelioma were treated with palliative mitomycin-C, vinblastine and cisplatin (MVP) chemotherapy. Eight of 39 patients (20%) achieved an objective partial response with a median duration of nine months; only five patients had progression of disease during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their symptomology with particularly good responses for pain. These benefits were independent of performance status. Resolution of symptoms was achieved in all responding patients within two treatment cycles. The treatment was well tolerated with only four patients developing grade 3 leukopenia (white blood cell reduction) and three with grade 3 nausea. MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic relief. These results should be the basis for further trials of MVP in the management of malignant mesothelioma with symptom control as a principal endpoint. "Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in malignant mesothelioma", Middleton, et al., Annals of Oncology, 9(3):269-73, March 1998.
COMPLETE REMISSION OF PERITONEAL MESOTHELIOMA WITH CHEMOTHERAPY IN JAPAN. A 71 year-old Japanese woman presented with a malignant abdominal mass and ascites (effusion and accumulation of serous fluid). The mass demonstrated widespread peritoneal dissemination, which therefore could not be resected surgically. Pathological findings suggested a malignant peritoneal mesothelioma. The patient showed remarkable response to combined chemotherapy with an accompanying intraperitoneal injection of cisplatin and etoposide and an intravenous injection of caffeine. However, owing to side effects, this regimen was discontinued. The patient was administered a combination drug of uracil and tegafur in addition to intraperitoneal injection of cisplatin as an outpatient. By the 223rd day after surgery, the tumor mass and ascites had completely disappeared according to computerized tomography scans. Chemotherapy was judged to have resulted in complete remission. Such marked response to chemotherapy is rare in an advanced malignant peritoneal mesothelioma. Eight months later, the tumor recurred in the pleura. Another regimen of cisplatin and CPT-11 was performed. However, this treatment proved ineffective. The patient subsequently died of respiratory failure due to the mesothelioma. "A case of malignant peritoneal mesothelioma showed complete remission with chemotherapy", Imada, et al., Japanese Journal of Clinical Oncology, 28(2):145-8, February 1998. A 71 year-old Japanese woman presented with a malignant abdominal mass and ascites (effusion and accumulation of serous fluid). The mass demonstrated widespread peritoneal dissemination, which therefore could not be resected surgically. Pathological findings suggested a malignant peritoneal mesothelioma. The patient showed remarkable response to combined chemotherapy with an accompanying intraperitoneal injection of cisplatin and etoposide and an intravenous injection of caffeine. However, owing to side effects, this regimen was discontinued. The patient was administered a combination drug of uracil and tegafur in addition to intraperitoneal injection of cisplatin as an outpatient. By the 223rd day after surgery, the tumor mass and ascites had completely disappeared according to computerized tomography scans. Chemotherapy was judged to have resulted in complete remission. Such marked response to chemotherapy is rare in an advanced malignant peritoneal mesothelioma. Eight months later, the tumor recurred in the pleura. Another regimen of cisplatin and CPT-11 was performed. However, this treatment proved ineffective. The patient subsequently died of respiratory failure due to the mesothelioma. "A case of malignant peritoneal mesothelioma showed complete remission with chemotherapy", Imada, et al., Japanese Journal of Clinical Oncology, 28(2):145-8, February 1998.
COMBINATION OF CISPLATIN AND PACLITAXEL SUPERIOR. The antitumor effectiveness of cisplatin, paclitaxel and suramin as single agents and in combination was evaluated in vivo against four lines of human pleural malignant mesothelioma xenografts in mice. Cisplatin was very effective against one line and also to a lesser degree against another line. Paclitaxel showed antitumor effects similar to cisplatin, being very effective in one line, and also showed good activity in another line. Suramin was basically inactive in all four lines. Cisplatin and paclitaxel were combined and evaluated against the same four lines of mesothelioma, with a result of more pronounced antitumor effect in all four cell lines. These results indicate that the combination of cisplatin and paclitaxel is superior to each agent alone, and deserves to be evaluated in patients with malignant mesothelioma. "Effectiveness of cisplatin, paclitaxel, and suramin against human malignant mesothelioma xenografts in athymic nude mice", Chahinian, et al, Journal of Surgical Oncology, 67(2):104-11, February 1998.
NOVEL CISPLATIN TREATMENT EFFECTIVE FOR PERITONEAL MESOTHELIOMA. Aggressive debulking of peritoneal mesothelioma combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity. Ten patients with peritoneal mesothelioma ranging in age from 15 to 57 underwent tumor debulking followed by CHPP. Medain follow-up time was ten months. There was no treatment-related mortality. In eight optimally debulked patients there is no evidence of recurrent disease clinically or by computerized tomography or magnetic resonance imaging scans. Seven patients with symptomatic ascites were completely palliated. CHPP with cisplatin is well tolerated with no significant regional toxicity. Because favorable cisplatin pharmocokinetics suggest the potential for enchanced tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma. "Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma", Ma, et al., Cancer Journal from Scientific American, 3(3):174-9, May-June 1997. Aggressive debulking of peritoneal mesothelioma combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity. Ten patients with peritoneal mesothelioma ranging in age from 15 to 57 underwent tumor debulking followed by CHPP. Medain follow-up time was ten months. There was no treatment-related mortality. In eight optimally debulked patients there is no evidence of recurrent disease clinically or by computerized tomography or magnetic resonance imaging scans. Seven patients with symptomatic ascites were completely palliated. CHPP with cisplatin is well tolerated with no significant regional toxicity. Because favorable cisplatin pharmocokinetics suggest the potential for enchanced tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma. "Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma", Ma, et al., Cancer Journal from Scientific American, 3(3):174-9, May-June 1997.
DIHYDRO-5-AZACYTIDINE TREATMENT FOR MALIGNANT MESOTHELIOMA. Malignant mesothelioma is a disease which does not readily yield to chemotherapy. Therefore, a multi-institutional Phase II trial aimed to demonstrate the efficacy of dihydro-5-azacytidine (DHAC) in the treatment of malignant mesothelioma. Forty-one patients with histologically confirmed malignant mesothelioma received 120-hour continuous infusions of DHAC 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. Conclusions: DHAC has definite antitumor activity. Caution regarding cardiac arrhythmias and pericardial effusion is necessary. "Dihydro-5-azacytidine in malignant mesothelioma. A phase II trial demonstrating activity accompanied by cardiac toxicity. Cancer and Leukemia Group B.", Vogelzang, et al., Cancer, 79(11):2237-42, June 1, 1997.