Keiichi Endo

Oral high-dose medroxyprogesterone acetate (MAP) in treatment of advanced breast cancer. A preliminary report of clinical and experimental studies.

SummaryMedroxyprogesterone acetate (MAP) in the treatment of advanced breast cancer has been regarded as a minor agent according to the previous reports when used at low doses (<500 mg/day). High doses of more than 500 mg which have come into use since 1973 give a response rate of over 40%, but sometimes cause gluteal abcess or induration because of daily intramuscular injections.In order to administer easily and to avoid the side effect, we have attempted to use oral administration in a daily dose of 1200mg (400 mg × 3). Of those 20 patients treated with oral high-dose MAP, 1 showed complete response, 6 showed partial response, 7 no change, and 6 progressive disease. As for site of lesion, 4 out of 6 (67%) in skin and 4 out of 16 (25%) in bone responded. Neither severe side effects nor abnormal laboratory data were seen.Then, we examined the blood levels of MAP in vivo by RIA in 9 patients. The blood level of MAP reached 39–250 ng/ml in 3 days and was maintained at least over 50 ng/ml for 1 or 2 months of continuous administration. Subsequently, we examined the effects of MAP on binding to ER in vitro. The inhibition of binding of estradiol-17β to ER was about 60% at 10−5 M MAP. The blood level of 50 ng/ml in vivo corresponds to about 1.3 × 10−5 M.

The clinicopathological significance of preoperative serum-soluble interleukin-2 receptor concentrations in operable non-small-cell lung cancer patients

BackgroundSerum-soluble interleukin-2 receptor (IL-2R) concentrations have been found to be elevated in cancer patients. However, the importance of this finding in patients with non-small-cell lung cancer (NSCLC) has not been previously established.MethodsPreoperative serum-soluble IL-2R concentrations were determined in 65 consecutive patients with operable NSCLC. The correlation of preoperative serum-soluble IL-2R concentrations with various clinicopathological features of this cancer was evaluated to clarify the clinical significance of this parameter.ResultsAlthough serum-soluble IL-2R concentrations were not significantly higher in operable NSCLC patients than in normal controls (P=.1180), serum-soluble IL-2R concentrations were significantly higher in patients with stage IIIB or IV disease than in normal controls (P=.0001). The presence of intrapulmonary metastasis was the only clinicopathological feature that was significantly correlated to serum-soluble IL-2R concentration (P=.0004). The sensitivity of serum-soluble IL-2R concentration in identifying the presence of intrapulmonary metastasis was 87.5%; specificity was 75%.ConclusionsElevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of intrapulmonary metastasis. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in the detection of the intrapulmonary metastasis preoperatively.

Breast-conserving therapy versus modified radical mastectomy in the treatment of early breast cancer in Japan

BackgroundBreast-conserving therapy has been widely utilized as a treatment option for women with early breast cancer. However, no randomized study comparing modified radical mastectomy and breast-conserving therapy has been conducted in Japan.MethodsTwo hundred and twenty-eight Japanese women with early breast cancer enrolled in the Gunma Breast Conserving Therapy Study between 1991 and 1994 were examined to determine whether there is any difference in disease-free survival or overall survival between radical mastectomy and breast-conserving therapy. After informed consent was obtained, a total of 119 patients underwent breast-conserving therapy and 109 underwent mastectomy.ResultsMastectomy was a more frequently utilized treatment than breast-conserving therapy in patients with clinical stage II lesions, older age, larger tumor size or shorter distance between tumor and nipple. The mean follow-up period for all patients was 81 months (median 86 months). There was no significant difference in overall survival or disease-free survival between breast-conserving therapy and mastectomy even after adjusting for the clinical stage of the disease. A multivariate analysis of tumor size, lymph node status, estrogen receptor status and operation method using the Cox proportion hazard model confirmed that only lymph node status was an independent prognostic factor.ConclusionBreast-conserving therapy is comparable to modified radical mastectomy in overall survival and disease-free survival.

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer

Abstract Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5′-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4′-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5′-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2–90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12–121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 ± weeks (range 12–82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Bilateral pneumothorax associated with lung and pleural metastases of breast cancer.

A rare case of bilateral pneumothorax in a 54-year-old woman with advanced breast cancer associated with lung and pleural metastases is presented. The patient was admitted to our hospital complaining of unexpected severe dyspnea. A chest X-ray showed bilateral pneumothorax associated with multiple lung metastases and pleural effusions, followed by immediate pleural drainage. Although air leak and effusions of the right lung were well controlled by the conservative management, massive air leaks of the left lung had continued for 40 days. Because of patients poor general status a surgical closure of the leaking site was selected using video-assisted thoracoscopic surgery techniques. Thoracoscopy revealed a ruptured bulla in the lower lobe (S6), thus, followed by a successful bullectomy with a stapling device. We speculate that multiple pleural metastasis may disturb the normal repair mechanism of the lung tissue and cause prolonged persistent air leaks.