A case report: effective trans-arterial neoadjuvant chemotherapy with docetaxel for a local advanced breast cancer patient

Recently, there have been some reports about the effectiveness of docetaxel for breast cancer patients who had polychemotherapy previously in vein. We report here a case of a 47-year-old woman, who had been diagnosed as local advanced breast cancer. She was given trans-arterial chemotherapy with docetaxel after four series of CEF (cyclophosphamide, epirubicin, fluorouracil) therapy resulted in PD (progressive disease). Local disease was successfully controlled, and she could undergo standard radical mastectomy.     

Preoperative chemotherapy followed by mastectomy for locally advanced breast cancer

Six patients with advanced local-regional breast cancer were reviewed. Five out of the six patients previously had had radiation therapy as part of the initial therapy. All patients had preoperative cycles of combination chemotherapy, either CMF or CAF. The two stage III patients had greater than 75% reduction in measurable tumor mass, which allowed a conventional modified radical or radical mastectomy to be performed. Both of these patients are now disease free at 26 and 27 months. The four stage IV patients had lesser operations following the chemotherapy (two simple mastectomies, one simple mastectomy plus axillary resection, and one axillary debulking). Reconstruction utilized advancement flaps in three patients and split-thickness skin grafts in the other. None of the patients had postoperative wound problems, and none of the patients had further problems with local cancer control. All patients had combination chemotherapy starting two to six weeks following surgery. Preoperative chemotherapy followed by surgery plays an important role in management of locally advanced stage III and stage IV breast cancer.     

Use of doxorubicin plus cyclophosphamide followed by docetaxel as adjuvant chemotherapy for breast cancer

We evaluated the feasibility and incidence of hematological toxicity in a series of 39 breast cancer patients treated at our institute with doxorubicin plus cyclophosphamide (AC) followed by docetaxel, using prophylactic G-CSF (pegfilgrastim). We prescribed G-CSF as secondary prophylaxis during the AC regimen and as primary prophylaxis during treatment with docetaxel. For the AC treatment, we recorded 6 cases of grade III (15.3%) and one case of grade IV (2.5%) neutropenia; we found one case of Grade IV anemia. For the docetaxel regimen, we registered one case of Grade IV (2.5%) neutropenia and three cases of Grade III leukopoenia without neutropenia. No patients experienced cardiac symptoms or baseline LVEF rate decrease. All patients concluded the programmed chemotherapy. Our experience shows the safety of docetaxel in combination with anthracyclines and the efficacy of prophylaxis with G-CSF in breast cancer adjuvant chemotherapy.     

Intra-arterial infusion chemotherapy with docetaxel for locally advanced breast cancer and inflammatory breast cancer

From 1998 to 2000, we performed neoadjuvant intra-arterial infusion chemotherapy using docetaxel (60 mg/m2) a few times with 5 patients with local advanced breast cancer and inflammatory breast cancer. Therapeutic effects included 3 cases of PR among the breast tumor patients and downstaging was obtained 2 cases. No critical side effects were found due to this chemotherapy. We could perform mastectomy in all the cases. We consider intra-arterial infusion using docetaxel to be highly effective with few side effects in cases of advanced breast cancer.     

Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.     

A phase II study of sequential docetaxel followed by doxorubicin/cyclophosphamide as first-line chemotherapy for metastatic breast cancer

This phase II study assessed the activity and toxicity profile of the sequential administration of 3 cycles of docetaxel (100 mg/m2 every 3 weeks) followed by 3 cycles of AC (doxorubicin/cyclophosphamide; 60/600 mg/m2 every 3 weeks) as first-line chemotherapy in 30 patients with metastatic breast cancer. The response rate was 60% after docetaxel and 73% after AC. This reflected an increase in the rate of complete response (from 7% after docetaxel to 17% after AC). The median duration of response was 10.5 months, and the median time to progression was 12.6 months. The median survival time had not been reached after a median follow-up of 23.2 months. The sequential treatment was generally well tolerated, with grade 3/4 neutropenia found in 20% and 14% of patients treated with docetaxel and AC, respectively. No cumulative myelosuppression was detected. The incidence of grade 3/4 nonhematologic toxicities was low. The sequential administration of docetaxel followed by AC showed a high antitumor activity and a good safety profile. The hematologic toxicity found is markedly lower than that found using concomitant chemotherapy with the same drugs. Our results support the design of phase III trials that directly compare a sequential schedule with a concomitant schedule of docetaxel plus AC (or with doxorubicin only), focusing on the toxicity profile.     

A case of hepatic arterial infusion chemotherapy with docetaxel for liver metastasis from breast cancer

We experienced a case of hepatic arterial infusion chemotherapy using docetaxel for liver metastasis, which showed no response to CEF therapy, from breast cancer. A 63-year-old woman had undergone modified radical mastectomy for right breast cancer (T2aN1bM0: Stage II) in October, 1995. Six-cycle CMF therapy and toremifene citrate (40 mg/day) were administered as adjuvant therapy, but multiple recurrent tumors in liver, lung, and local site were detected in February 1997. Six-cycle CEF therapy was given for recurrent disease and there was a complete response for lung and local recurrence, but no change in liver metastasis. Chemoendocrine therapies using 5'-DFUR or CMitF in addition to TAM and fadrozole hydrochloride hydrate had developed progressive disease for liver metastasis. A catheter and port kit were operatively inserted and implanted in March 1998. Hepatic arterial infusion of docetaxel (30-40 mg/body/month, one hour administration) was repeated 4 times, once in our clinic. Leukopenia, general fatigue and fever, which were mild and did not require any treatment, appeared as side effects. This treatment reduced multiple liver metastatic sites on abdominal CT finding and was thought to be a partial response. However, the patient had multiple brain metastasis and died on August 2, 1998. While docetaxel, even by systemic administration, has a 36-77% response rate for liver metastasis, arterial infusion might have a good response and mild side effect with a lower dose than by intravenous administration.     

多西他赛联合表阿霉素与多西他赛联合顺铂一线治疗晚期乳腺癌的临床研究

目的 评价多丙他赛联合表阿霉素(TE方案)与多西他赛联合顺铂(TP方案)一线治疗局部晚期或转移性乳腺癌患者的疗效和安全性.方法 88例患者按2:1随机进入TE组和TP组.TE组患者药物剂量为多西他赛75 mg/m2,表阿霉素60 mg/m2;TP组患者药物剂量为多西他赛75mg/m2,顺铂75 mg/m2. 21 d为1个周期,2个周期末评价近期疗效及安全性.结果 TE组可评价近期疗效者55例,其中CR 3例,PR 26例,SD 22例,PD 4例.TP组可评价近期疗效者27例,其中CR 1例,PR 16例,SD 9例,PD 1例.TE组和TP组近期有效率分别为48.3%和60.7%(P=0.2788),临床受益率分别为85.0%和92.9%(P=0.4899),中位肿瘤进展时间(TTP)分别为10个月和8个月(P=0.7119).Ⅲ、Ⅳ度不良反应主要为中性粒细胞减少,TE组和TP组发生率分别为66.7%和53.6%(P=0.2373);其次为脱发,TE和TP组分别为30.0%和10.7%(P=0.0508).结论 TE方案与TP方案一线治疗局部晚期或转移性乳腺癌的疗效和安全性相当.     

A case of advanced breast cancer leading to DIC after chemotherapy

We reported a case of DIC who was administered FEC90 (5-FU 1,000 mg/body, epirubicin 170 mg/body, cyclophosphamide 1,000 mg/body) for advanced breast cancer. A 55-year-old woman was referred to our hospital with lumbago. There was a huge tumor in her left breast (10x10 cm) and bone scintigraphy showed multiple bone metastasis, so she was treated with FEC90. Before the third course, DIC occurred. The patient was then treated with FOY and heparin, and the DIC was resolved. We think the DIC of this case was related with tumor lysis syndrome. Febrile neutropenia has been occasionally emphasized during chemotherapy, but due care must be taken for lymphocyte depletion during treatment.     

A case of advanced breast cancer that responded remarkably to chemotherapy

The case of a 49-year-old woman with axillary lymph nodes, multiple bone and multiple lung metastases from advanced breast cancer is reported. The patient responded remarkably to combination chemo- and endocrine-therapy. This patient was discharged after receiving 2 cycles of cyclophosphamide, pirarubicin and 5'-DFUR, while continuing to receive daily oral doses of 5'-DFUR and MPA. The patient experienced few adverse effects during chemotherapy. The patient enjoys an improved quality of life. This combined regimen has been confirmed to be an effective treatment for patients in advanced stages of breast cancer.     

Prospective phase II study of neoadjuvant doxorubicin followed by cisplatin/docetaxel in locally advanced breast cancer

The objective of this study is to evaluate the efficacy and safety profile of the doxorubicin followed by cisplatin/docetaxel as primary chemotherapy for patients with locally advanced breast cancer (LABC). For this evaluation, 59 patients with LABC (T2–T4, N0–N2, M0) received three cycles of doxorubicin, followed by three cycles of cisplatin/docetaxel and followed by definitive surgery and locoregional radiotherapy with or without tamoxifen. The primary end point was pathologic complete response (pCR) in breast and axilla. Fifty-nine patients were evaluable for analysis: median age: 41 years, premenopausal: 68%, median tumor size: 6.0 cm (4–10), Stage IIB: 32% and IIIA/IIIB: 68%, both ER/PR positive: 53%, Her2/neu (3+) by IHC staining: 29%. Clinical complete response was seen in 44%, and clinical partial response was seen in 56%. Breast conserving surgery was performed in 44%, and MRM in 56%. pCR in the breast was 30.5%, in axilla was 37%, and pCR in both breast and axilla was 24%. Overall at follow-up of 60 months, the disease-free (DFS) and overall survival (OS) were 70 and 82%, respectively. The DFS and OS of patients who achieved complete pathologic response in breast and axilla were 78 and 100%, respectively, while 14 patients relapsed of which 46% were Her2 positive. Sequential combination of doxorubicin followed by docetaxel/cisplatin is a safe, feasible, and active combination, which offers the possibility of conservative surgery and is associated with high clinical and pathologic response rates, with promising and encouraging survival outcomes.     

长春瑞滨联合顺铂治疗晚期乳腺癌的临床观察

目的探讨长春瑞滨联合顺铂治疗经紫杉醇＋蒽环类联合化疗失败的局部晚期乳腺癌和复发转移乳腺癌的疗效及安全性。方法10例采用紫杉醇＋蒽环类化疗耐药的局部晚期乳腺癌和31例手术后紫杉醇＋蒽环类辅助治疗的转移性乳腺癌患者,应用长春瑞滨（25mg／m^2,第1,8天,静脉滴注）、顺铂（30mg／m^2,第1—3天,静脉滴注）化疗,对其疗效及不良反应进行分析。结果全组患者完全缓解6例（14．6％）,部分缓解17例（41．5％）。不良反应以骨髓抑制、消化道反应常见。结论长春瑞滨联合顺铂方案对蒽环类和（或）紫杉醇耐药的乳腺癌疗效较好,值得临床进一步研究。     

多西他赛加顺铂诱导化疗联合同期放化疗局部晚期非小细胞肺癌的临床观察

目的 评价TP方案诱导化疗联合同期放化疗局部晚期非小细胞肺癌的近期疗效和不良反应。方法 病理证实的局部晚期非小细胞肺癌86例,随机分成同期放化疗联合TP方案诱导化疗(ICCRT) 组和单纯同期放化疗(CCRT) 组。放疗均采用调强放疗。治疗结束后比较两组疗效、生存率和不良反应。结果 86例患者的随访率为100%。ICCRT组和CCRT组的有效率分别为80%和70%(χ²=1.26,P=0.261),1、2、3年总生存率分别为85%和65%、50%和40%、44%和33%(χ²=3.90,P=0.048),主要不良反应白细胞减少(43例和32例,χ²=3.48,P=0.062)、放射性食管炎(26例和20例,χ²=0.12,P=0.730)、血红蛋白减低(26例和16例,χ²=2.34,P=0.126)和放射性肺炎(13例和9例,χ²=0.37,P=0.541)。结论 ICCRT能明显提高局部晚期非小细胞肺癌的总生存率,且与CCRT相比并不增加局部不良反应。     

SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first-line chemotherapy for ovarian cancer

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.     

Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer

BackgroundTo evaluate capecitabine–docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC).Patients and methodsPatients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m² twice daily, days 1–14, plus docetaxel 36 mg/m², days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The primary end point was pathologic complete response (pCR) rate, evaluated separately in HER2-negative and HER2-positive cohorts. Secondary end points included clinical response rates and tolerability.ResultsThe pCR rate was 15% [95% confidence interval (CI) 7–28] in 53 patients receiving XT and 40% (95% CI 26–55) in 50 patients receiving HXT. After neoadjuvant therapy, 50 patients receiving XT and 45 receiving HXT underwent surgery. No unexpected toxicity was observed: the most common grade ≥3 adverse events were diarrhea/mucositis (30% and 20%, respectively) and grade 3 hand–foot syndrome (11% and 6%, respectively). Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort.ConclusionNeoadjuvant XT (HXT in HER2-positive disease) is highly effective in inoperable LABC, demonstrating pCR rates of 15% and 40%, respectively. This non-anthracycline-containing regimen offers obvious benefits in early disease, where avoidance of long-term cardiotoxicity is particularly important.     

Preoperative chemotherapy for advanced breast cancer

Preoperative chemotherapy was initiated for breast cancer in an effort to decrease the number of viable cancer cells that were released into the blood stream during surgical procedure. This possibility was substantiated by several observations made in animal experiments and clinical studies. Preoperative chemotherapy was also given to render the advanced disease amenable to surgical intervention. In one report, systemic chemotherapy (CAF) for advanced breast cancer produced a response rate of 86% preoperatively, facilitating subsequent mastectomy and a postoperative 5-year survival rate of 52%. However no definite conclusion has yet been obtained as to the prognostic significance of systemic chemotherapy give preoperatively, and further comparative studies are therefore required. Preoperative intra-arterial chemotherapy as an induction therapy was administered to patients with locally advanced breast cancer including inflammatory breast cancer, the treatment developed in Japan. In our institute, intra-arterial chemotherapy with ADR or MMC plus 5-FU resulted in a marked decrease in the size of primary and lymph node lesions with 82% CR + PR. Histological examination of resected specimens also revealed that 35% of the patients had no viable cancer cells remaining in their lesions. Five-year and 10-year survival rates were 57% and 41%, respectively, compared with 24% and 18%, respectively for historical controls. Patients showing better local responses to intra-arterial chemotherapy had longer survival time with less frequent local recurrences. Some other studies also indicated improved survival in locally advanced breast cancer as a result of preoperative intra-arterial chemotherapy. Preoperative chemotherapy including systemic administration is a promising modality for advanced breast cancer.     

Neoadjuvant and adjuvant chemotherapy with doxorubicin and docetaxel in locally advanced breast cancer

Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 intravenously infused over 1 hour every 21 days with granulocyte colony-stimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.