Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to evaluate the antitumor effect of two drug combinations in disseminated breast cancer. Eighty-one patients divided into two groups entered this nonrandomized study. Group 1 included 32 patients treated with CAP combination: Cyclophosphamide--200 mg/m2 on days 1, 3 and 5 + adriamycin--40 mg/m2 on day 1 + cisplatin--30 mg/m2 on days 1, 3 and 5. Group 2 included 49 patients treated with CAF combination: Cyclophosphamide--100 mg/m2 on days 1 to 14 + adriamycin--30 mg/m2 on days 1 and 8 + 5-fluorouracil--500 mg/m2 on days 1 and 8. All patients had at least 2 courses of chemotherapy. In Group 1 the remission rate was 50% (16 patients) including 3 complete (9%) and 13 partial remissions (41%). In Group 2 the remission rate was 39% (18 patients) with 8 complete (16%) and 10 partial remissions (23%). The analysis of duration of the remissions showed a tendency towards longer duration after treatment with CAP combination (25 versus 15 months for the complete remissions, and 14 versus 11 months for the partial remissions).
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PMID:Antitumor effect of combination of cyclophosphamide, adriamycin and platinum (CAP) versus cyclophosphamide, adriamycin and 5-fluorouracil (CAF) in metastatic breast cancer. 176 85

Due to the favourable results previously obtained with cisplatin in breast cancer (54% response rate), we studied a second-generation platinum analogue, carboplatin, in patients with previously untreated breast cancer. A total of 20 patients were entered in the study and all were evaluable. The median age was 57 years and all patients were in menopause. Karnofsky scores of 80-100 and 40-70 were registered in 14 and 6 cases, respectively. The predominant metastatic site was soft tissue in 12 subjects, visceral organs in 5 and bone in 3; 14 patients had greater than 2 metastatic sites. Carboplatin was given i.v. at a dose of 400 mg/m2 on day 1, with a 3-week rest period. In 13 patients who did not respond or whose disease recurred after carboplatin treatment, the CMFVP, CAP or FAC regimen was given as second line treatment. Carboplatin activity was observed in 4 patients [2 complete remissions (CRs) and 2 partial responses (PRs)], for a response rate of 20% (4/20); the 2 PRs were observed in soft tissue and bone and the 2 CRs, in lung, liver and bone. Remission lasted 2-10 months (mean, 4 months). CMFVP given as second-line chemotherapy to 13 patients produced 7 PRs (7/13, 54%). Toxicity was moderate, producing no drug-related deaths. Anemia (grade I-II) was recorded in seven patients; grade I-II leukopenia, in six; and grade III-IV leukopenia in two (median leukocyte nadir, 1,600/mm3). Thrombocytopenia was observed in three cases (grades I, II and III; median platelet nadir, 47,800/mm3). Unpleasant nausea/vomiting was pronounced (12 cases of grade III-IV) in 19 subjects. There were no cases of neuro- or nephrotoxicity. Due to permanent myelosuppression, no more than five cycles could be given. Our study showed that, unlike cisplatin, carboplatin given at a dose of 400 mg/m2 has low antitumorigenic activity in breast cancer patients and produces pronounced myelotoxicity. Additional first-line chemotherapy studies using carboplatin are needed to define the antitumorigenic activity of this platinum analogue.
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PMID:Carboplatin activity in untreated metastatic breast cancer patients--results of a phase II study. 199 4

Exposure to multiple non-cross-resistant drugs should increase cell kill and the chance of achieving more complete and partial responses. Our earlier study in breast cancer showed that second-line CAP (cyclophosphamide, adriamycin, cis-platinum) treatment was not cross-resistant to the CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) regimen and produced a 51% response rate. These facts initiated a phase II study which used an alternating CMFVP/CAP regimen. Altogether, 49 patients entered the study and 45 were evaluated (greater than 2 cycles). The CMFVP regimen consisted of cyclophosphamide (200 mg/m2 on days 1, 2, 3, 4 and 5), methotrexate (30 mg/m2 on days 2 and 4), 5-fluorouracil (500 mg/m2 on days 1, 3 and 5), vincristine (1.4 mg/m2 on days 1 and 5), and prednisolone (40 mg p.o. on days 1-5), and was alternated with the CAP schedule (300 mg/m2 cyclophosphamide on days 1, 3 and 5, 50 mg/m2 adriamycin on day 1, and 30 mg/m2 cis-platinum on days 1, 3 and 5). Overall response was high, and 37 patients out of 45 responded (82%), with a 28% CR rate (13/45). A particularly high response rate was observed in soft tissues (86%, 18/21) and visceral organs (84%, 16/19). Only 1 patient progressed (3%). The duration of remission was 4-21+ months (median, 12 months). Six of 13 CR patients were still disease free 15 months after the treatment was stopped. The duration of survival was 5-25+ months (median, 15+ months). Toxicity was moderate (myelosuppression in 53% of patients, mainly grade I-II; stomatitis in 11%, except for 100% alopecia and 90% nausea and vomiting). One drug-related death (bone marrow aplasia) was recorded. The high antitumorigenic activity of the alternating regimen used is encouraging and may call for a randomized study for the ultimate evaluation of this treatment approach.
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PMID:cis-platinum-based alternating non-cross-resistant chemotherapy as a first-line treatment in metastatic breast cancer. A phase II study. 225 93

Platinum-based combination chemotherapy regimens (CAP or CMF + cisplatin) were used for the treatment of disseminated breast cancer. Response rate for the CAP regimen was 47.5%. The most frequent side-effects were nausea, vomiting, nephrotoxicity and myelosuppression. Relationship between survival and response was identified.
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PMID:[Chemotherapy of disseminated forms of breast cancer using platinum derivatives]. 234 95

Fourteen evaluable patients with gynecologic adenocarcinoma (7 ovarian, 4 endometrial, 2 peritoneal and one breast cancer) were treated with ifosfamide (1 g/m2 X 5 days), adriamycin (50 mg/m2) and cisplatin (50 mg/m2) combined chemotherapy (IAP). All the patients had measurable disease, and three were refractory cases who had received prior chemotherapy including two CAP (cyclophosphamide, adriamycin and cisplatin). To avoid hemorrhagic cystitis induced by ifosfamide, uroprotective mesna (400 mg/body X 3) was used following ifosfamide infusion. The 5-day schedule of IAP treatment brought a 100% response rate in these patients. Complete responses were observed in 3 patients and lasted 6, 10 and 12 months. Partial responses were achieved in 11 patients including two with CAP refractory ovarian cancer, although the remission in previously treated patients was of short duration. Hematologic side effects of the IAP regimen were severe, showing grade 4 leucopenia in 85.7% of the patients, and it required maximal anti-infection treatments. Mesna resulted in microhematuria in only one patient. Despite high age of the patients (mean age: 60.1 years) in this study, CNS (central nervous system) toxicities associated with ifosfamide and mesna treatment were minimal. The results suggested that the IAP combination therapy was effective and acceptable in the control of gynecological adenocarcinomas.
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PMID:Treatment of gynecological adenocarcinomas with a combination of ifosfamide, adriamycin and cisplatin. 313 35

Thirty patients with metastatic carcinoma of the breast were treated with a combination of cyclophosphamide, Adriamycin (doxorubicin), and peptichemio (CAP) as an induction regimen, and maintenance regimen consisting of thiotepa, methotrexate, and 5-fluorouracil (TMF). Twenty-four patients were evaluable. Thirteen patients achieved an objective response for a response rate of 54.0% (complete remission plus partial remission). Median duration of response was 9.5 months (0-32+). The CAP regimen had severe myelotoxicity that led to dose reductions in 67% of patients. Furthermore, 50% of the patients required delay (greater than 28-day interval) in chemotherapy courses because of myelosuppression, and peptichemio had to be discontinued in seven patients. The CAP chemotherapy as an induction regimen for metastatic breast carcinoma resulted in underutilization of Adriamycin, and proved to be inferior to other Adriamycin-containing regimens. Although peptichemio used as a single agent had significant activity against breast cancer, it was not suitable for prolonged use in conjunction with other myelosuppressive agents. However, it may have a role in second-line therapy of metastatic breast cancer in conjunction with nonmyelosuppressive agents. The authors were unable to test the efficacy of non-cross-resistant maintenance therapy with TMF in this trial.
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PMID:Combination chemotherapy of metastatic breast carcinoma with cyclophosphamide, adriamycin, and peptichemio. 623 Oct 92

It is possible to examine about 95% of tumors using the short-term tumor test from Volm et al. The test results are available within one day. In 89 cases of ovarian tumor stages III and IV, the clinical progress using different chemotherapies could be compared with the results of the uridine-adriamycin-test. In the uridine-adriamycin-test, 82% of the cases with sensitive tumors showed either a remission or at least no change. Resistant tumors were, however, in 56% of cases progressive. Whilst combination largely of proliferation-inhibiting cytostatic drugs such as CF- or CAP-therapy showed a good relationship between the behavior of the tumors in vitro and their response to the cytostatic therapy a similar relationship under CP-therapy with a high cisplatin dosage, could not yet be proved, although until now in only a small number of cases. In vitro sensitive ovarian carcinomas stage III with the histological grade II or III, have a better prognosis under chemotherapy than resistant carcinomas. The importance attached to the short-term tumor test from Volm in the cytostatic therapy of ovarian carcinomas, must be similarly assessed as that of steroid receptors to the endocrine therapy of breast cancer.
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PMID:[Experiences with Volm's short-term tumor test in the primary treatment of ovarian carcinoma]. 637 39

We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.
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PMID:A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer. 638 59

Cisplatin containing regimens as first-line, second-line or as a third-line chemotherapy were administered in 26 and 36 patients, respectively. The overall response rate in patients on first-line chemotherapy was 53.9%, in patients on second or third-line chemotherapy 30.6%. The differences both in overall and disease-free survival between patients on first-line and on second/third-line chemotherapy were statistically significant in favor of women treated with first-line chemotherapy (p = 0.05). Hematologic and nonhematologic toxicities were mild to moderate and were more pronounced in patients on second and third-line chemotherapy. The overall response rate, DFS and OS were significantly better and longer in the group of patients treated with "bolus" CDDP in comparison to the group of patients treated with CVI CDDP. Our results confirm the activity of cisplatin-containing regimens (mainly CAP schedules) in patients with advanced breast cancer not only as a first-line therapy but also in heavily pretreated patients by chemotherapy and/or radiation therapy and endocrine manipulation.
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PMID:The role of cisplatin in chemotherapy of advanced breast cancer. 787 Feb 19

We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the hormone-dependent MCF7 cell line, within the pS2 gene 5'-flanking region, we detected two major DNase I hypersensitive sites, induced by estrogens and/or IGFI: pS2-HS1, located in the proximal promoter and pS2-HS4, located -10.5 Kb from the CAP site, within a region that has not been cloned. The presence of these two DNase I hypersensitive sites correlates with pS2 expression. Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable chromatin structural changes over the pS2 regulatory region, suggesting that the two transduction-pathways converge to a unique chromatin target. In two cell lines that do not express pS2, MDA MB 231, a hormone-independent cell line that lacks the estrogen receptor alpha, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor alpha, there was only one hormone-independent DNase I hypersensitive site. This site, pS2-HS2, was located immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive sites were present in the 5'-flanking sequences of the cathepsin D gene, which is regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3, located at positions -2.3 Kb and -3.45 Kb, respectively, were both hormone-independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA MB 231 cells, that express cathepsin D constitutively, we detected an additional strong hormone-independent DNase I hypersensitive site, catD-HS4, located at position -4.3 Kb. This region might control the constitutive over-expression of cathepsin D in hormone-independent breast cancer cells. All together, these data demonstrate that a local reorganization of the chromatin structure over pS2 and cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells.
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PMID:Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines. 992 10


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