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Biomedical subjects

C K Tashima

Publications and source records attributed to C K Tashima.

At least 37 records · Page 2Linked to original sources

Combination chemotherapy with vincristine and methotrexate for advanced refractory breast cancer.

Eighteen patients with advanced breast cancer refractory to combination chemotherapy with 5-FU, Adriamycin, Cytoxan (FAC) were treated with methotrexate 30 to 40 mg/m2 iv and vincristing 1.5 mg/m2 iv at weekly intervals. Of 17 evaluable patients, 4 (23%) achieved a partial remission with a median duration of remission of 6 months and a median survival of 10 months. In another seven of seventeen patients (41%) the disease remained stable. Toxicity was minimal.

Adult↗

Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer.

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.

Adult↗

Male breast cancer: a natural history study.

Eighty-seven cases of male breast cancer seen over a 30-year period were reviewed. The overall observed and corrected five-year survival rates of 42% and 53% correspond well with the results in other series. Factors predicting disease-free interval and survival included size of primary lesion, ipsilateral axillary status, and presence of ulceration, which appear to be similar to those observed for female breast cancer. Eighteen patients (21%) had a second primary tumor (seven with cutaneous malignancies) and were of an older age group with a higher incidence of positive family history of breast cancer as well as other tumors. The overall prognosis of breast cancer in males does not appear to be less favorable than that in females.

Adult↗

Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG.

One hundred five patients with metastatic breast cancer were treated with 5-fluorouracil, Adriamycin, cyclophosphamide and BCG (FAC-BCG). The results were compared to those observed in a group of 44 patients treated with FAC chemotherapy alone. Although the overall response rates were similar (76% for FAC-BCG and 73% for FAC), the duration of remission was of 9 months for FAC and 14 months for FAC-BCG (p = 0.008). Similarly, survival of responding patients treated with FAC-BCG was significantly longer (24 months) than that observed in the chemotherapy alone treated group (15 months). There was no difference in survival or duration on study for nonresponders. Analysis of response rates by known prognostic factors was unrewarding. The duration of remission and survival, however, were significantly longer for patients with bone soft tissue involvement than for patients with visceral metastasis. Similarly patients with 1 or 2 metastatic sites survived significantly longer than those with more than 3 organ sites involved (p = 0.02). This chemotherapeutic combination is highly effective in inducing remissions. In addition, nonspecific immunotherapy with BCG appears to prolong duration of remission and survival for responding patients.

Adult↗

Combined chemoimmunotherapy and radiation therapy of inflammatory breast carcinoma.

Thirty-two patients with a diagnosis of primary inflammatory breast carcinoma were treated with combination chemoimmunotherapy consisting of 5-fluorouracil, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (FAC) plus BCG followed by radiation therapy. This group of patients was compared to a group of 32 consecutive historical controls treated with radiation therapy alone. The estimated mean disease-free interval for the FAC-BCG group was 16 months, compared to 9 months for the radiation therapy alone group (P less than 0.01). The estimated median survival for the FAC-BCG treated group was 24 months, compared to 18 months for the radiation therapy alone group (P = less than 0.03). The combined modality approach consisting of chemoimmunotherapy and radiation therapy significantly improved the disease-free interval and survival of patients with inflammatory breast carcinoma.

Adult↗

Adjuvant chemoimmunotherapy following regional therapy for isolated recurrences of breast cancer (stage IV NED).

A combination of 5-fluorouracil, Adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in breast cancer patients following surgical excision and/or radiation of first site of recurrent disease. In a group of 68 patients treated with FAC-BCG, the estimated proportion remaining free of disease at 2 years from first recurrence was 69%, compared to 24% in 60 historical control patients (P less than 0.01). Estimated 2-year survival rate from first recurrence was 85% for the FAC-BCG patients and 78% for the controls (P = 0.07). This regimen has significantly prolonged the disease-free interval from the first recurrence, but additional follow-up is needed to determine its effect on long-term survival.

Antineoplastic Agents↗

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.

BCG Vaccine↗

High-dose methotrexate for advanced breast cancer.

High-dose infusions of methotrexate with citrovorum factor rescue were evaluated in 27 patients with advanced recurrent breast cancer who had previously been treated with various Adriamycin-containing regimens. Eight of 27 patients (29%) achieved objective tumor regression with a median duration of response of 26 weeks. Nineteen patients had previously received standard doses of methotrexate (less than 50 mg/m2/dose), while eight patients had had no prior exposure to methotrexate. The response rates observed in these two groups of patients were similar. Except for two drug-related deaths, toxic effects were acceptable. Myelosuppression was mild, transient, and noncumulative. Gastrointestinal toxic effects did not appear to be dose-related and were mild in most instances. Central nervous system dysfunction with lethargy, fatigability, confusion, and disorientation was the most significant toxic effect of this high-dose methotrexate therapy and was observed in six (22%) of the patients. In two patients treatment with this program was discontinued because of the development of renal dysfunction. High-dose methotrexate with citrovorum factor rescue appears to be an effective regimen in patients with advanced refractory breast cancer. However, in view of the enormous cost necessitated by this treatment approach, we do not feel further studies would be worthwhile.

Age Factors↗

Ifosfamide versus cyclophosphamide in combination drug therapy for metastatic breast cancer.

A combination of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) was compared to a combination of 5-FU, adriamycin, and ifosfamide (FAI) in the treatment of metastatic breast cancer. All patients in the FAC and FAI groups also received nonspecific immunotherapy with bacillus Calmette-Guérin (BCG) and levamisole. Of 117 evaluable FAC patients, 19 (16%) achieved complete remission and 66 (56%) achieved partial remission. In the FAI group, eight of 49 (16%) evaluable patients achieved complete remission and 24 (50%) achieved partial remission. The response rates, durations of remission, and survival were similar in both groups. The combination of two immunotherapeutic agents (BCG and levamisole) did not have an additive effect since their results were similar to our previous experience with FAC-BCG and FAC-levamisole. In the FAI group, 25% of the patients had hematuria, while none of the patients in the FAC group had urinary complications. Nausea and vomiting were more severe in FAI-treated patients and some patients required iv fluids to correct dehydration. Ifosfamide in combination with 5-FU and adriamycin was more toxic than and not superior to cyclophosphamide.

Adult↗

Phase II study with sequential L-asparaginase and methotrexate in advanced refractory breast cancer.

The combination of sequential L-asparaginase and methotrexate (MTX) was evaluated in 33 patients with advanced refractory breast cancer. There were nine partial responses and one complete response, giving an overall response rate of 30% and a median duration of response of 8 months. Five of 17 patients (28%) who had received prior MTX at doses of less than 50 mg/m2 responded. Toxicity was acceptable. Moderate-to-severe stomatitis occurred in most patients and was the dose-limiting factor. Myelosuppression was minimal until the dose of MTX was escalated to greater than or equal to 180 mg/m2. The maximum tolerated dose of MTX was 280 mg/m2 and the median toxic dose was 220 mg/m2. These data indicate a selective "rescue" from MTX damage to normal target tissue by L-asparaginase. The antitumor effect observed even in patients who had been previously exposed to conventional doses of MTX suggests a possible improved therapeutic index of MTX given sequentially with L-asparaginase in this combination.

Adult↗

Diabetes insipidus and breast cancer.

Diabetes insipidus, resulting from metastatic involvement of the neurohypophysial system, is a rare complication of breast cancer. This review examined the clinical features, metastatic pattern, and radiological and postmortem findings of 39 breast cancer patients with this complication. All patients had polyuria and polydipsia, and all had evidence of advanced metastatic breast cancer. A high incidence of meningeal carcinoma carcinomatosis and/or sellar metastases was observed. In view of the anatomical proximity of the posterior pituitary to the dura mater and the sella turcica, our findings suggest that metastases to the neurohypophysis can occur not only as a result of hematogenous dissemination of malignant cells, but also from direct tumor extension and/or invasion from adjacent structures. Although satisfactory symptomatic relief can be obtained with vasopressin tannate, complete resolution of the diabetic insipidus syndrome was evident only in those patients who had achieved control of the underlying breast disease.

Adult↗

Mitomycin-C and megestrol acetate in treatment of breast cancer refractory to hormonal and combination chemotherapy.

Fifty patients with breast cancer refractory to endocrine manipulation and/or combination chemotherapy were treated with mitomycin-C 20 mg/m2 I.V. every 4-6 weeks and megestrol acetate 160 mg daily. Of 48 evaluable patients, 4% achieved complete remission (CR), 23% had partial remission (PR). Median duration of response for CR and PR was 7 months. Non-responders had a median survival of 2 months. The difference in survival of responders (both CR and PR) and non-responders was statistically significant at p less than 0.01 level. Attenuated doses of mitomycin-C were administered at increasing intervals due to cumulative myelosuppressive toxicity.

Adult↗

Intensive postoperative chemoimmunotherapy for patients with stage II and stage III breast cancer.

For the past 34 months, a combination of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in stage II and III breast cancer patients with positive axillary nodes. In the group of 131 patients receiving FAC-BCG, the estimated proportion remaining disease-free at 2 years from surgery was 91% compared to an estimated 69% in a group of 151 historical control patients (p less than .01). This advantage was statistically significant in all subgroups except for patients with primary tumor less than 3 cm and for patients with less than 4 positive nodes. Estimated 2-year survival rates were 9,6% for FAC-BCG patients and 86% for control (p = .02). Treatment was well tolerated. Adjuvant FAC-BCG seems effective in prolonging disease-free interval and early survival in patients with stage II and III breast cancer. Its long term efficacy will require longer follow-ups.

Adult↗