Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this pilot study was to estimate the toxicity and response rate of an alternating chemotherapeutic program in chemotherapy-naive metastatic breast cancer patients. Treatment consisted of regimen A (given days 1-28): cyclophosphamide 100 mg/m2 PO days 1-14, doxorubicin 30 mg/m2 i.v. days 1 and 8, and 5-fluorouracil 500 mg/m2 i.v. days 1 and 8 (CAF regimen); regimen B (given days 29-56): dibromodulcitol 135 mg/m2 p.o. days 30-39, mitoxantrone 9 mg/m2 i.v. day 29, and vincristine 1.2 mg/m2 i.v. (maximum 2.0 mg) day 29 (DMV regimen); and regimen C (given days 57-84): thiotepa 12 mg/m2, doxorubicin 45 mg/m2 and vinblastine 4.5 mg/m2 all i.v. on day 57. There were 27 eligible patients with a median age of 51 years (range 34-78). On 14 episodes the leukocyte count fell to less than 1 X 10(9)/L during the first six cycles of treatment (14% of 99 cycles). There were no treatment-related deaths. Common non-life-threatening toxicities included thrombocytopenia, anemia, vomiting, and alopecia. Despite having no drugs in common, the leukocyte and platelet nadirs after CAF correlated with the nadir counts after DMV (r values of 0.6829 and 0.5892, respectively; p = 0.01). Among the 23 patients with measurable and/or evaluable disease there were five complete responses (22%) and nine partial responses (39%), with a median time to treatment failure of 29 weeks. The overall median survival was 19 months.
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PMID:A pilot study of three sequential chemotherapeutic regimens in metastatic breast cancer. 189 99

This trial was conducted to determine if the reported superiority of tamoxifen (TAM) plus prednisolone (PRDLN) over TAM alone in postmenopausal women with metastatic breast cancer could be corroborated. A total of 326 patients were randomized on a double-blind trial to TAM (10 mg twice daily) plus placebo or TAM plus PRDLN (5 mg twice daily). Six patients (2%) were disqualified. Considering 256 patients with measurable or evaluable disease, objective responses were seen in 48 (38%) of 126 TAM patients and 61 (47%) of 130 TAM plus PRDLN patients (chi-square, P = 0.15). Considering all 320 evaluated patients, median time to disease progression was 11 months for TAM and 10 months for TAM plus PRDLN (log rank, P = 0.81), and median survival time was 35 and 32 months, respectively (P = 0.40). Covariate analyses showed no significant association between treatment and outcome. Weight gain and edema were significantly greater with TAM plus PRDLN. The addition of PRDLN to TAM is not advocated for the management of postmenopausal women with metastatic breast cancer.
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PMID:A double-blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic. 204 50

Forty-six postmenopausal women with either locally advanced or metastatic breast cancer were treated with the aromatase inhibitor CGS 16949A in three different daily doses (0.3 mg, 0.6 mg and 0.9 mg total daily dose). 41 patients (89%) were pretreated by endocrine treatment for metastatic disease; 30 of these 41 were also pretreated with chemotherapy. Of the remaining 5 patients (11%) 3 were previously treated with chemotherapy alone and 2 were not pretreated. Evaluable sites of disease were: skin and soft tissue (including local recurrence) in 34, bone in 31, lung in 14 and viscera in 13 instances, respectively. 1 PR (3%) and 9 stable diseases (24%) were observed in the 37 patients assessable for response. All but two of these results were observed in the 0.9 mg group. Time to progression was 14 months for the patient showing a PR, and the median time to progression for those with stable disease was 6 months (range 6 to 23 months). Plasma estradiol and estrone levels were measured in patients receiving the daily dose of 0.6 mg (n = 4) and 0.9 mg (n = 15). The estrone levels decreased from a mean of 23.1 pg/mL (SD 17.1) to 10.5 pg/mL (SD 6.6) in the 0.6 mg-group and from 21.2 pg/mL (SD 18.9) to 9.1 pg/mL (SD 5.5) in the 0.9 mg-group within 4 days of drug administration (p less than 0.0001 from baseline in both groups, with no significant difference between doses).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer--a phase I study. 215 May 91

A randomized trial was performed to determine relative efficacy and toxicity of two first-line combination chemotherapy regimens in women with metastatic breast cancer: CFP (cyclophosphamide, 5-fluorouracil, prednisone) and CMFP (cyclophosphamide, 5-fluorouracil, methotrexate, prednisone). Both regimens have reported efficacy in this setting but differ in dosages and scheduling of the agents they have in common. Three hundred thirty-six women with no prior chemotherapy for metastatic disease were eligible and evaluable, and 309 had either measurable or evaluable disease and were assessable for objective response. Responses were seen in 65 of 153 (42%) on CFP and 83 of 156 (53%) on CMFP (two-sided P = 0.06). Median durations of response were 7.1 months for CFP and 8.5 months for CMFP (log-rank, two-sided P = 0.67). Considering all 336 patients, the median times to disease progression were 4.7 months for CFP and 6.2 months for CMFP (log-rank P = 0.31) and median survivals were 15.2 and 14.9 months, respectively (log-rank P = 0.88). Covariate analysis did not alter these findings. Median leukocyte nadirs were 1800 for CFP and 1500 for CMFP, with 22% and 21%, respectively, having nadirs less than 1000/microliters. Emesis was more frequent on CFP (49%) than on CMFP (26%) but was severe in only 7% and 5%, respectively. It is concluded that despite a higher response rate on CMFP and some differences in toxicities including a higher reported incidence of emesis on CFP, there was no substantial difference in efficacy or tolerability between the two regimens.
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PMID:Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. 264 21

The Eastern Cooperative Oncology Group (ECOG) conducted a pilot study of combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil plus aminoglutethimide (250 mg three times daily with hydrocortisone supplementation of 40 mg daily) as primary therapy for estrogen receptor-positive or unknown advanced breast carcinoma to assess whether these agents can be safely combined and to provide a preliminary estimate of response rate. A total of 47 patients, 45 with metastatic breast cancer and two with stage IV disease who were rendered clinically disease free following surgical resection of chest wall recurrence, were treated. Leukopenia and mucositis were the most frequent toxicities requiring dose reduction, but only five patients (10.6%; 95% confidence interval, 1.8-18.4%) experienced life-threatening leukopenia (less than 1000/mm3) at some point during their therapy. Neurologic side effects attributed to aminoglutethimide, predominantly lethargy, were reported in less than one-third of patients, and rarely required dose reduction. One elderly patient developed clinical hypothyroidism during the first 3 months on therapy and experienced a cardiac arrest at home while receiving supplemental thyroid hormones. The overall complete plus partial response rate in 45 patients was 55.5% (95% confidence interval, 41-70%). Among 16 patients with measurable disease, the complete plus partial response rate was 75% (95% confidence interval, 54-96%). The complete plus partial response rate in 29 patients with nonmeasurable but evaluable disease was 45% (95% confidence interval, 27-63%) and an additional 14% had improvement in bone pain. Eight patients electively discontinued chemotherapy after 7-24 months of therapy, but continued aminoglutethimide. The median time to disease progression is 462 days (15.4 months); 25% of patients died by 552 days (18.4 months), and the median duration of survival is predicted to be 889 days (29.6 months). We conclude that aminoglutethimide can be combined with this doxorubicin-based regimen with acceptable toxicity and an overall response rate which is similar to that observed on prior ECOG trials with cyclophosphamide, doxorubicin, and 5-fluorouracil.
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PMID:A phase II evaluation of combination chemotherapy plus aminoglutethimide in women with metastatic or recurrent breast carcinoma. An Eastern Cooperative Oncology Group Pilot Study. 317 53

The aim of this study was to compare the treatment efficacy of mitomycin-C plus tamoxifen (MT) to adriamycin, dibromodulcitol and tamoxifen (DAT) in previously treated patients with metastatic breast cancer. Thirty-two patients with measurable or evaluable disease were entered on the study. Twenty-three were prospectively randomized to receive DAT (Group 1) or MT (Group 2). Nine patients with prior exposure to adriamycin were directly assigned to receive MT (Group 3). Thirty-one patients were evaluable for response and toxicity. The hematological toxicities were comparable among the three treatment groups. DAT gave more nausea and vomiting than MT. One patient developed irreversible fatal congestive heart failure while receiving DAT. The response for Group 1 was 5/11, Group 2, 3/12, and Group 3, 3/8. The duration of response for patients in Group 1 was 455+, 315, 251, 239, 231 days, in Group 2 it was 328+, 144+, 119, and in Group 3 it was 35+, 84, and 112 days. The median time to treatment failure did not differ significantly between Group 1 (114 days), 2 (83 days) and 3 (61 days) (p = 0.24). The median survival time was similar among the three groups (p = 0.41). This pilot study suggests that MT and DAT are both effective treatment programs in patients with metastatic breast cancer who have failed prior chemotherapy regimens.
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PMID:A pilot study of mitomycin-C and tamoxifen (MT) versus dibromodulcitol, adriamycin, and tamoxifen (DAT). 718 Aug 30

We treated 39 women with newly diagnosed stage IV breast cancer with a new regimen of mitoxantrone 18 mg/m2 on days 1, 29, 57, vincristine 1.4 mg/m2 (maximum 2.0 mg) on days 1, 8, 15, 22, 29, 36, 43, 50, and 5-fluorouracil 375 mg/m2 on days 15-20, 43-47, 71-75 with leucovorin modulation 500 mg/m2 before each 5FU infusion (MVF). This regimen was utilized as an initial cytoreductive or induction program for these patients prior to high-dose intensification with autologous stem cell rescue. Ten patients (25%) obtained a clinical complete response and six patients (15%) obtained a partial response for an overall response rate of 40%. In addition, 10 patients had evaluable disease that was improved or stable (primarily bone and/or bone marrow metastases) after MVF induction. Thus, 26 patients (65%) were eligible for high-dose intensification with autologous stem cell rescue after MVF induction. Toxicity was primarily a mild mucositis and more commonly peripheral neuropathy. MVF therapy is an active treatment program for metastatic breast cancer but the neurotoxicity makes it difficult to recommend for widespread use.
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PMID:Mitoxantrone, vincristine, and 5-fluorouracil with leucovorin modulation as induction chemotherapy prior to high-dose intensification in metastatic breast cancer. 801 57

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an effective drug in the treatment of metastatic breast cancer (MBC). In the salvage setting, 5-fluorouracil (5-FU) and folinic acid have proved to be effective against MBC as well. Recent preclinical data suggest that paclitaxel plus 5-FU has additive cytotoxicity. Given these observations, we initiated a phase II trial in which 38 women with MBC have been treated with a combination of all three drugs. All patients are currently evaluable for toxicity and 34 are evaluable for response. All women had histologically proven and assessable disease. Patients with prior exposure to paclitaxel were ineligible. Patient characteristics include a median age of 51 years (age range, 31 to 73 years) and a median performance status of 1 (range, 0 to 2). Thirty-three patients have received prior chemotherapy, of whom 23 had adjuvant chemotherapy only. Fifty-eight percent of the patients (22 of 38) had received prior doxorubicin or mitoxantrone; four patients had only hormonal therapy. Four patients had bone-only disease, and three patients had lymphangitic spread or cytologically positive pleural effusion as the only evaluable disease. Treatment consisted of paclitaxel 175 mg/m2 over 3 hours (day 1 only), followed by folinic acid 300 mg over 1 hour, followed by 5-FU 350 mg/m2 on days 1 to 3. Patients received standard paclitaxel premedications. To date, 175 cycles have been administered (median cycle length, 29 days; median number of cycles per patient, five). Toxicities included grade 3/4 infections in nine cycles (5%), grade 3/4 mucositis in three cycles, grade 3/4 nausea/vomiting in three cycles, grade 1 paresthesias in 12 patients (32%), alopecia 100%, and 17 cycles (10%) associated with dose reduction. Based on Cancer and Leukemia Group B toxicity criteria, arthralgia/myalgias were modest and graded mild (32 cycles), moderate (nine cycles), or severe (two cycles). There were two major hypersensitivity reactions, prompting removal of those patients from further protocol treatment. Four patients are unassessable for response due to hypersensitivity reactions (two) and unevaluable disease (two). Among the 34 patients evaluable for response, there were three complete responses, 18 partial responses, one minor response, nine stable disease, and three progressive disease (response rate, 62%). Responses were seen in patients who had received prior doxorubicin or mitoxantrone (11 of 22 patients) and in anthracycline/naive patients (10 of 16 patients). Responses were observed in all metastatic sites: soft tissue, viscera, and bone. Paclitaxel/5-FU/folinic acid appears to be an effective and well-tolerated outpatient regimen for women with MBC, even after failure of anthracycline-containing therapy.
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PMID:Paclitaxel and 5-fluorouracil in metastatic breast cancer: the US experience. 862 38

Salvage chemotherapy for relapsed and refractory metastatic breast cancer is a challenging issue for oncologists. At our institution, the combination of mitomycin-C, vinblastine and cisplatin (MVP) is used for treatment. The records of 19 consecutive patients with refractory metastatic breast cancer treated with MVP between April 1992 and October 1995 were reviewed. The regimen consisted of mitomycin-C 6 mg/m2, vinblastine 6 mg/m2 and cisplatin 60 mg/m2, repeated every 3 to 4 weeks. The median age of patients was 49 years (range, 35-71 yr). All patients had clinically measurable or evaluable disease and a Karnofsky's performance status greater than or equal to 50%. The median number of prior chemotherapy regimens was two (range, 1-4). Eighteen (94.7%) patients had previously received an anthracycline/anthracenedione-containing regimen, and seven (36.9%) had progression of disease during these therapies. Sixteen patients had two or more sites of metastasis and 17 patients had visceral disease. The median duration of follow-up was 26 months. A mean of 3.5 courses (range, 1-7) was administered. One patient was lost to follow-up after one course of treatment. Of the remaining 18 patients, two complete and five partial responses were observed, for a total response rate of 37% (range, 17-61%, 95% CI). One of the partial responders had disease progression during anthracycline treatment. Treatment-related toxicities were relatively well tolerated. There were no treatment-related deaths. The median duration of response was 3 months (range, 2-11 mo). The median overall survival was 7 months (range, 1-32 mo). Our data suggest that the MVP regimen is an effective palliative treatment for patients with refractory metastatic breast cancer.
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PMID:MVP (mitomycin-C, vinblastine, cisplatin) salvage chemotherapy for relapsed and refractory metastatic breast cancer. 908 Jul 56

Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2; III, 24 mg/m2; IV, 32 mg/m2; and LV, 300 mg, followed by FU, 350 mg/m2, on days 1-3. Filgrastim was given at 5 micrograms/kg/day subcutaneously on days 4-13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as the dose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts: IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts < or = 20,000/microL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%) achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.
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PMID:Mitoxantrone dose augmentation utilizing filgrastim support in combination with fixed-dose 5-fluorouracil and leucovorin in women with metastatic breast cancer. 915 Aug 98


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