Conventional dose CAF therapy versus low dose adriamycin therapy in the treatment of advanced breast cancer

A controlled randomized trial was conducted to compare the effectiveness of a conventional dose of CAF therapy with that of a low dose of adriamycin (ADR) therapy for the treatment of advanced breast cancer. The doses of medication for the conventional CAF therapy were 100 mg/body of cyclophosphamide (CPA) p.o. daily for two weeks, 30 mg/m² of ADR and 500 mg/m² of 5-fluorouracil (5-FU) i.v. on days 1 and 8 for induction, and 200 mg/body of 5-FU and 20 mg/body of tamoxifen (TAM) p.o. daily for maintenance. Those for the low dose ADR therapy were 15 mg/ m² of ADR i.v. at two-week intervals for one year and 200 mg/body of 5-FU and 20mg/body of TAM p.o. daily. Eighty patients were entered in this trial. All patients were randomly divided into two groups with stratification for estrogen receptor status. Of 78 patients among them, 38 undergoing the CAF therapy and 40 undergoing the low dose ADR therapy, were evaluated for efficacy assessment. The background factors analyzed were well balanced in both groups. The response rate was 47% (6 CR, 12 PR out of 38) in the CAF group and 43% (3 CR, 14 PR out of 40) in the low dose ADR group. There was no significant difference in response rates and survival rates as determined by the Kaplan Meier method between the two groups. The CAF therapy had significantly more toxicity than the low dose ADR therapy. Therefore, it was concluded that this low dose ADR therapy can be regarded as a treatment of choice for advanced breast cancer.     

The effects of multiple combination chemotherapy with vincristine,cyclophosphamide (Endoxan), methotrexate, 5-fluorouracil,adriamycin and prednisolone (VEMFAH) for advanced breast cancer

Thirty-eight patients with advanced breast cancer were treated with the 'VEMFAH' multiple-drug combination chemotherapy, consisting of vincristine (V), cyclophosphamide (Endoxan; E), methotrexate (M), 5-fluorouracil (F), adriamycin (A), and prednisolone (H). Disease response was evaluated by the UICC criteria. Among the 35 evaluable cases, 4 complete responses (CR), 23 partial responses (PR), 2 cases of no change (NC), and 6 of progressive disease (PD) were observed. The response rate (CR + PR) was 77.1%. The median duration of response was 52 weeks (8-192 weeks) or 12 months. In 32 patients who received more than two courses of therapy the 50% survival time of responders was 27.0 months, which was significantly longer than the 10.3 months of nonresponders (P less than 0.05). Except for 2 patients who developed myocardial damage, the therapy was never terminated because of side effects. Cumulative cardiotoxicity was not apparent in this study. This multiple-drug combination chemotherapy with 'VEMFAH' is concluded to be an effective treatment for advanced and disseminated breast cancer.     

Caf versus caf plus medroxyprogesterone acetate for treatment of liver metastases of breast cancer

A controlled randomized trial was conducted to compare the effectiveness of a CAF therapy including cyclophosphamide (CPA), adriamycin (ADR) and 5-fluor-ouracil (5FU) with that of CAF plus medroxyprogesterone acetate (MPA) therapy including CPA, ADR and 5FU plus MPA for the treatment of liver metastases from breast cancer. A total of 34 patients with unresectable liver metastases from breast cancer were divided into two treatment groups (CAF and CAF + MPA) with stratification for estrogen receptor status. The response rate was 13% (2 PR in 16 patients) for CAF therapy and 22% (1 CR and 3 PR in 18 patients) for CAF plus MPA therapy. There was no significant difference in response rates, median survival periods and survival rates between the two treatment groups. However, CAF therapy had significantly more toxicity than did CAF plus MPA therapy. The findings of this study suggested that CAF plus MPA therapy is a well-tolerated and effective treatment for patients with liver metastases of breast cancer.     

High-dose combination chemotherapy with autologous bone marrow transplantation in breast carcinoma

Twelve patients with breast carcinoma were treated with high-dose combination chemotherapy supported by autologous bone marrow transplantation (ABMT). Seven of them had advanced metastatic disease and received 12 cours of A treatment, response rate (CR +PR) was 71.5% (CR: 1, PR: 4, NC: 2 and PD: 0) and it should be noted that all 4 patients who had received adriamycin 150 mg+5-fluorouracil 1,500 mg divided in two consecutive days or equivalent high-dose of other chemotherapeutic regimen responded (CR: 1 and PR: 3). To the therapy Five other patients received ABMT-supported adjuvant chemotherapy because of high risk of recurrence. One of them died of unrelated cause and other 4 are free of disease at 11, 14, 17 and 17 months following this treatment. A major toxicity was of myelosuppression and nadirs of neutrophils were 100-1,800 on days 9-19 (median: 400 on day 12), neutrophils recovered rather rapidly to levels of greater than or equal to 1,000, greater than or equal to 1,500 and greater than or equal to 2,000 by day 15, 16 and 17, respectively. High-dose combination chemotherapy with ABMT seemed quite effective in advanced breast carcinoma and a similar approach in adjuvant setting has also been suggested.     

High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer

Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.     

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目的 观察甲酰四氢叶酸钙(CF)联合5-氟尿嘧啶(5-Fu)治疗晚期乳腺癌的疗效和安全性.方法 选择既往经过蒽环类、紫杉类等药物治疗无效的晚期乳腺癌31例,中位年龄48.0岁(27～66岁).采用CF联合5-Fu化疗方案治疗.CF[150 mg/(m2·d)]+ 5-Fu[600 mg/(m2·d)],连用5天,每天静脉滴注不少于12h,每4周为一周期.观察有效率及不良反应.结果 完全缓解2例(6.5％),部分缓解7例(22.6％),病情稳定6例(19.4％),进展16例(51.6％).总有效率为29.0％,临床获益率为48.4％,其中激素受体阴性患者更能获益(P＜0.05).中位有效期为2.3月(95％CI:1.1～4.1),中位生存期为9.5月(95％CI:4.7～14.8).15例(48.4％)生活质量改善,6例(19.4％)稳定,10例(32.3％)下降.不良反应主要是胃肠道反应(11例)、骨髓抑制(4例)和口腔炎(9例).结论 CF+ 5-Fu联合静脉滴注二线治疗晚期乳腺癌疗效确切,不良反应可控,患者易于耐受,可以作为复发转移的晚期难治性乳腺癌的解救治疗.     

High-dose medroxyprogesterone acetate versus oophorectomy as first-line therapy of advanced breast cancer in premenopausal patients.

Forty premenopausal patients with advanced breast cancer entered a prospective and randomized study in which high-dose medroxyprogesterone acetate (HD MAP) and oophorectomy (OPX) were compared. All the patients were first treated for advanced disease. Twenty-two patients received HD MAP (1,000 mg b.i.d. p.o.) and 18 patients received OPX. Complete remission (CR) was achieved in 2 (9%) in the HD MAP group and in 2 (11%) in the OPX group for a duration of 20-24 and 30-54 months respectively. Partial remission (PR) was achieved in 10 (45%) patients in the HD MAP group and in 4 (22%) patients in the OPX group for a median duration of 9 and 7 months respectively. The objective response rates (CR + PR) were 55% for the HD MAP group and 33% for the OPX group (p = 0.17). Ten patients who received OPX as first-line treatment received HD MAP when the disease progressed and were evaluable for response: PR was achieved in 6 patients (2 responders and 4 nonresponders to OPX) for a median duration of 5 months. Two out of 4 patients who received OPX at progression after objective response to HD MAP presented PR. HD MAP induced a significant decrease in pain intensity and, compared to OPX, a more frequent improvement was induced in performance status. No difference was observed between the two groups in terms of overall survival. This study shows that HD MAP is an active treatment in premenopausal patients with advanced breast cancer and that it can induce a response in some patients resistant to OPX.     

CAF方案和CTF方案治疗中晚期乳腺癌的疗效观察

目的 比较CAF和CTF方案治疗晚期乳腺癌的疗效和毒副作用。方法 97例Ⅲ～Ⅳ期乳腺癌患者被随机分为2组,A组53例,用含阿霉素(ADM)的CAF方案治疗4～6周期;B组44例,用含吡柔比星(THP)的CTF方案治疗4～6周期。结果 A组CR 5例,PR 23例,有效率53.8％;B组CR 5例,PR 20例,有效率56.8％。两组疗效差异无显著性(P>0.05)。不良反应中白细胞下降率,两组差异无显著性(P>0.05),胃肠道反应发生率两组差异有显著性(P<0.05),脱发及心脏毒副反应发生率两组差异有显著性(P<0.01)。结论 CTF方案疗效与CAF方案相当,但患者更易耐受,特别是脱发和累积性心脏毒副反应要远低于CAF方案,因此THP治疗晚期乳腺癌患者是高效、安全的。     

A study on the efficacy of combination chemoendocrine therapy consisting of cyclophosphamide, adriamycin, UFT, and tamoxifen for advanced or recurrent breast cancer]

The efficacy of the combination chemoendocrine therapy CAUT against advanced and recurrent breast cancer was examined. One course of this therapy lasted 3 weeks and consisted of adriamycin (i.v.) at 30 mg/m2 on day 1, cyclophosphamide (p.o.) at 65 mg/m2 and UFT (p.o.) at 300 mg/m2 on days 1-14, and tamoxifen (p.o.) at 20 mg/body on days 1-21. Twenty patients were enrolled, of whom 19 were eligible including seven with advanced cancer and 12 with recurrent cancer. One patient achieved CR, ten PR, three NC, and five PD, for a response rate of 58% (95% CI: 29-87%). The response rates according to type of lesion were 73% (8/11) for the soft tissue, 38% (3/8) for the bone, 20% (1/5) for the lungs and pleura, and 50% (2/4) for the liver. Adverse events with a severity of grade 3 or more included a reduction in WBC in six patients (31.6%), a reduction in RBC in one (5.3%), alopecia in four (21.1%), and severe general fatigue in one (5.3%). One patient experiencing a grade 4 reduction in WBC, and one of five patients experiencing a grade 3 reduction with a fever, recovered after treatment with G-CSF. The other four patients recovered following suspension of administration. This therapy is considered useful, exhibiting a high response rate and relatively slight adverse effects.     

老年进展期乳腺癌患者应用CEF新辅助化疗的疗效观察

目的 探讨应用CEF方案（环磷酰胺＋表柔比星＋氟尿嘧啶）新辅助化疗对老年进展期乳腺癌患者的治疗效果。方法35例Ⅲ期老年乳腺癌患者行麦默通穿刺活检，均经病理检查确诊后，按CEF方案行新辅助化疗。化疗2—4个疗程不等。化疗后均行手术治疗。结果新辅助化疗后完全缓解5例，部分缓解26例，有效率88．6％，无临床进展病例。化疗的毒副作用主要表现为脱发、骨髓抑制和胃肠道反应。进展期乳腺癌降期的所有患者均接受手术治疗。随访中1例患者死于肺心病，2例死于肺转移，1例死于肝转移，2例发生骨转移。结论对身体状况较好的进展期老年乳腺癌患者新辅助化疗并不一定是化疗的禁区，部分患者仍能取得较好的疗效。     

吉西他滨联合顺铂治疗晚期乳腺癌的临床观察

目的探讨吉西他滨联合顺铂方案治疗一线治疗后失败的晚期乳腺癌的临床疗效和不良反应。方法对入组的32例经病理证实的既往治疗后进展的乳腺癌患者,应用吉西他滨1000mg/m2,静滴,第1天、第8天;顺铂25mg/m2,静滴,第2～4天;联合化疗,每21天为1个周期。至少2个周期后评价疗效。结果 32例患者中,部分缓解(CR)3例(9.4%),完全缓解(PR)15例(46.9%),疾病稳定(SD)9例(28.1%),疾病进展(PD)5例(15.6%),总有效率(CR+PR)56.3%,临床获益率为84.4%。中位疾病进展时间(TTP)8.7个月。1年生存率62.5%。不良反应以骨髓抑制、消化道反应最为常见。结论应用吉西他滨联合顺铂治疗既往化疗后进展的晚期乳腺癌,疗效较好,不良反应较轻,值得临床推广应用。     

High-intensity therapy versus low-intensity therapy in advanced breast cancer patients

The aim of this study was to evaluate the significance of response to the first two cycles of FEC (5-fluorouracil, 4-epirubicin, cyclophosphamide) in patients with advanced breast cancer. A total of 99 patients entered the study. They showed either high risk criteria and were previously untreated or showed low risk criteria and were pretreated by hormonal therapies. Eighty-two patients were evaluable. In 22 (27%) who had disease progression despite two cycles of FEC, further therapeutic attempts proved ineffective, the median survival being 2.8 months. The remaining patients responded either by stable disease (SD, n = 29; 35%), by partial or by complete remission (PR, CR, n = 31; 38%). These 60 patients were randomized to two regimes of maintenance therapy: FEC every 3 weeks or LMF (leukeran, methotrexate, 5-fluorouracil) every 6 weeks. The subsequent course of the disease was not different in both arms. It was neither influenced by the quality of early response, i.e. SD, PR, CR, nor by the intensity of chemotherapy. The prognostic impact of early response to two cycles of FEC proved to be higher than other prognostic parameters in the patients examined. Thus, early response may serve as a valid guide to adapt maintenance chemotherapy in individual patients with advanced breast cancer.     

A phase III randomized trial of cyclophosphamide,mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide,adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer

Summary One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m²) or mitoxantrone (12 mg/m²) associated with 5-fluorouracil (600 mg/m²) and cyclophosphamide (600 mg/m²) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m² day 1, Vbl 5 mg/m² days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer. M-Vbl treatment is useful as second-line treatment in patients with prior adriamycin exposure.     

Successful treatment of pleuritis carcinomatosa using combination therapy of 5'-DFUR, MPA and CPA as maintenance therapy

A 44-year-old female patient with inoperable, local advanced left breast cancer was treated with 3 cycles of high dose CAF therapy followed by combination therapy of 5'-DFUR, MPA and CPA. The patient was discharged after receiving 3 cycles of high-dose CAF therapy and continued to receive daily oral doses of 5'-DFUR (800 mg), MPA (800 mg), and CPA (100 mg) for 15 months. After 3 cycles of high-dose CAF therapy, tumor marker (CEA, CA 15-3) levels were reduced. Six months later, after 3 cycles of high-dose CAF therapy, the tumor marker levels were within the normal range. No serious side effects were observed during chemotherapy. The patient enjoyed a good quality of life. We thus confirmed that this combination regimen was effective as a maintenance therapy for local advanced breast cancer.     

Successful chemo-endocrine therapy for multiple bone metastases and myelophthisis caused by occult breast carcinoma

We report a 55-year-old postmenopausal woman with occult breast carcinoma with multiple bone metastases and myelophthisis in whom complete response (CR) was achieved with chemo-endocrine therapy. At the time of admission, she had anemia and left axillary lymph node enlargement, with extremely high levels of serum tumor markers and no breast mass on physical examination or on a mammogram. Roentgenograms and bone scintigrams showed multiple bone, lung, and pleural metastases. Bone marrow biopsy and aspiration cytology from the left axillary lymph node revealed an invasion of adenocarcinoma cells. On immunohistochemical staining, the cancer cells were positive for estrogen receptor (ER), progesterone receptor (PgR), and gross cystic disease fluid protein-15 (GCDFP-15). CR was induced with a combination chemotherapy of doxorubicin, cyclophosphamide, and 5-fluorouracil (CAF), and has been maintained with sequential docetaxel administration with endocrine therapy. Her performance status (Eastern Cooperative Oncology Group) improved from 4 to 0. This patient represents a very specific and rare case in whom a primary tumor could not be detected despite severe advanced breast carcinoma, and in whom CR was achieved by chemo-endocrine therapy. Received: October 21, 1999 / Accepted: July 28, 2000     

Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer.

PURPOSE: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIalpha gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. EXPERIMENTAL DESIGN: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIalpha and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. RESULTS: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIalpha amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIalpha amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIalpha (9 patients) was also associated with favorable response (P = 0.021). CONCLUSIONS: Coamplification of erbB-2 and topoisomerase IIalpha is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIalpha biology.     

Evaluation of efficacy and safety of first-line docetaxel/cisplatin/5-FU combined therapy for advanced esophageal cancer

We retrospectively evaluated the efficacy and safety of a first-line combination chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil (DCF therapy) in nine patients with advanced esophageal cancer. Dose administrated were 75 mg/m2 of Docetaxel on day 1, 75 mg/m2 of CDDP on day 1, and 750 mg/m2 of 5-FU on day 1-5. Complete response (CR) in two patients (22. 2%), partial response (PR)in three patients ( 33. 3%), and no change (NC) in four patients (55. 6%) were shown for main lesions, while CR in one (11. 1%), PR in five (55. 6%), and NC in three (33. 3%) were shown for lymph node metastases. Response rates of the DCF therapy were 55. 6% for main lesions and 66. 7% for lymph node metastases. Five patients who achieved PR or CR underwent esophagectomy with lymph node dissection. Toxicity from DCF therapy was grade 3 or 4 emergent adverse events (77. 8% of neutropenia, 55. 6% of febrile neutropenia, and 55. 6% of anorexia). DCF therapy improved the response rate in esophageal cancer patients, but resulted in some increase in toxicity. Prospective study with prevention of toxicity should be planned in order to evaluate first-line DCF therapy for advanced esophageal cancer.     

PCMF与CAF联合化疗治疗晚期乳腺癌疗效观察

我院从１９９４年到１９９５年１２月，用ＰＣＭＦ和ＣＡＦ联合化疗方案治疗晚期乳腺癌４８例，效果满意。ＰＣＭＦ方案的有效率为６６．７％（１６／２４），其中ＣＲ为２９．２％（７／２４），ＰＲ为３７．５％（９／２４）。ＣＡＦ方案的有效率为５８．３％（１４／２４），其中ＣＲ为２０．８％（５／２４），ＰＲ为３７．５％（９／２４）。两种方案疗效无显著差别（Ｐ＞０．０５）。中位缓解期分别为７和８个月，两种方案相近。     

Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial.

Adriamycin is of noteworthy efficacy in the treatment of metastatic breast cancer. Its role in combination regimens is under investigation. One hundred seventy-five women with advanced breast cancer were entered into a prospectively randomized trial comparing two five-drug regimens. Regimen CMFVP consisted of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), vincristine (V), and prednisone (P). Regimen CAFVP was identical but substituted Adriamycin (A) for methotrexate. Twenty-seven patients were disqualified; 148 were evaluable. With CMFVP the complete response rate (CR) was 11%, and the partial response rate (PR) was 46%; with CAFVP, CR was 13% and PR was 45%. Duration of response tended to be slightly longer for patients on the Adriamycin arm. The median survival for CR and PR patients with CMFVP was 20.2 months, which was shorter (p = .07) than the 33 month median survival with CAFVP. Although statistical significance was not reached at the 5% level, the increased survival of responders on the Adriamycin regimen supports the data of other studies which suggest that first line combination chemotherapy in advanced breast cancer should include Adriamycin.     

多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床观察

目的：观察多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床疗效及不良反应。方法：回顾性分析40例转移性乳腺癌患者的化疗资料,采用国产多西他赛75mg/m2,表柔比星70-90mg/m2静脉滴注,环磷酰胺500mg/m2每3周1次。观察每次化疗后的不良反应,完成4个疗程后观察疗效。结果：全部病例均按计划完成4个周期的化疗。完全缓解（CR）3例,部分缓解（PR）20例,稳定（SD）12例,进展（PD）5例。总有效率（CR＋PR）为57.5%,控制率（CR＋PR＋SD）87.5%。主要不良反应为中性粒细胞减少、恶心、呕吐、腹泻等。结论：多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌临床疗效较好,不良反应患者可以耐受。