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.     

Intra-arterial infusion chemotherapy with epirubicin for advanced breast cancer

Thirty-two patients with locally advanced or disseminated breast cancer were treated with preoperative intra-arterial infusion chemotherapy with epirubicin (30 mg/m2, day 1, 4, 7). The results were as follows: 1) the response rate (CR + PR) was as high as 71.9% (23/32) in the primary lesions. Marked degenerative changes were, also, histologically observed in 22 cases (68.8%). 2) As for side effects, mild grade of leukopenia and hair loss were frequently encountered in 75.0% and 62.5%, respectively. Gastrointestinal disorders, however, was extremely rare (6.3%). 3) Follow-up time was not long enough, but considerable survival advantages were suggested. The author confirmed that intra-arterial infusion chemotherapy with epirubicin was an efficacious modality for the treatment of advanced breast cancer.     

Two cases of stage IV breast cancer with locally advanced lesion treated by intra-arterial infusion chemotherapy using implantable reservoir

Intra-arterial infusion chemotherapy was used for 2 cases of Stage IV breast cancer with locally advanced lesions using implantable reservoir. The first case is a 64-year-old female who had multiple bone metastases with locally advanced breast lesion. A total dose of 220 mg ADM was injected via reservoir at outpatient department. The other case is a 66-year-old female who had multiple bone metastases with locally advanced breast lesions. A total dose of 235 mg ADM was injected via reservoir. After obtaining satisfactory response of local lesions, a standard radical mastectomy was performed for both cases. It was concluded that this method was useful for controlling locally advanced lesions of Stage IV breast cancer and beneficial for patient QOL.     

Intra-arterial infusion chemotherapy for breast cancer

Intra-arterial infusion chemotherapy has a significant effect in down-staging locally advanced breast cancer by providing a high dose intensity. It is also used for the treatment of liver metastasis. A better response rate and lower incidence of adverse effects are reported when patients are treated with intra-arterial infusion chemotherapy than with systemic chemotherapy using the same dose of the same drugs. Recent advances in devices such as access ports and portable infusion pumps make it possible to perform intra-arterial infusion chemotherapy repeatedly and safely. However, it remains uncertain whether or not intra-arterial infusion chemotherapy can improve the prognosis of cancer patients because of the lack of data from phase III trials. Accordingly, further studies including combined use of systemic chemotherapy are mandatory to the control of micrometastases outside the target organ.     

Intra-arterial infusion chemotherapy for locally advanced breast cancer using implantable reservoir connected with catheter inserted in recurrent radial artery

Intra-arterial infusion chemotherapy through a catheter incubated at the recurrent radial artery and connected to an implantable reservoir was performed in eight patients with supraclavicular lymph node metastasis including four locally advanced recurrent breast cancers and two inflammatory breast cancer. Clinical response in breast cancer patients was 1 CR, 3 PR, 1 NC, and 1 PD. There was no complication related with catheter insertion. Therefore from the aspect of quality of life, this system was considered useful for treatment of advanced breast cancer, especially locally advanced recurrent breast cancer.     

动脉化疗联合三维适形放疗治疗局部晚期胰腺癌的临床疗效

目的探讨动脉化疗联合三维适形放疗治疗局部晚期胰腺癌的疗效和安全性。方法 20例局部晚期胰腺癌采用吉西他滨（1 000 mg/m^2）区域性动脉灌注结合静脉化疗联合三维适形放疗治疗。放疗采用常规分割,1.8～2.0Gy/次,1次/天,5次/周,放疗剂量95%PTV45～50 Gy/25次。结果 20例患者全部完成治疗计划,原发灶完全缓解率为5.0%,部分缓解率为65.0%,总有效率为70.0%。临床获益率为80.0%。中位生存期为13个月,1、2年总生存率分别为56.2%、19.6%。1～2级白细胞下降发生率为80.0%,3级为20.0%;1～2级急性胃肠道反应发生率为90.0%,3级为5.0%。结论区域性动脉灌注化疗联合三维适形放疗是治疗局部晚期胰腺癌的1种有效方法。     

Clinicopathological estimation of intra-arterial infusion chemotherapy of locally advanced breast cancer

The effect of intra-arterial infusion chemotherapy with adriamycin as a preoperating procedure was analyzed clinicopathologically in 30 cases with locally advanced breast cancer. A clinical response rate of 53.3% was obtained by the treatment and remarkable degenerative changes of tumor cells were noted histologically in the primary lesions. But there was no relationship between histological therapeutic effect and regression rate in tumors. A recurrence rate showed a higher correlation with histological therapeutic effect in comparison with clinical therapeutic effect. Especially, non-necrosis type that tumor cells were still alive mainly in the vessels showed significantly a higher recurrence rate in comparison with a central necrosis type or focal necrosis with fibrosis and hyalinization type. The local regional recurrence rate of patients receiving intra-arterial infusion chemotherapy was lower than that of patients, as the historical controls, receiving no therapy before operation. But prognostically, there was no significant difference in a survival rate between both groups. So, after operation, other alternative or multidisciplinary adjuvant chemo-endocrine therapy seems to be necessary for improving the survival rate.     

Neoadjuvant intra-arterial infusion chemotherapy combined with hormonal therapy for locally advanced breast cancer

To determine the efficacy of combined neoadjuvant intra-arterial infusion chemotherapy and hormonal therapy for treating locally advanced breast cancer, we compared the outcomes of patients with or without this therapy, and also assessed histologic response. Ninety-four patients with locally advanced breast cancer (stage IIIa, 56; stage IIIb, 38). Nineteen stage IIIa and 17 stage IIIb patients received intra-arterial plus hormonal therapy while 37 stage IIIa and 21 stage IIIb patients with similar ages and follow-up durations did not. Treated patients received intra-arterial epirubicin plus oral medroxy-progesterone. Five-year disease-free survival rates were 77.5% for intra-arterially treated and 33.0% for other patients in stage IIIa, and 70.5% for intra-arterially treated and 38.1% for other patients in stage IIIb. Five-year overall survival rates were 94.4% for intra-arterially treated and 61.7% for other patients in stage IIIa, and 90.9% for intra-arterially treated and 56.3% for other patients in stage IIIb. Ten-year overall survival rates in stage IIIb were 90.9% for treated and 22.5% for other group patents. All differences were statistically significant (p<0.05). Good histologic response to intra-arterial therapy was seen in 75% of the primary tumors and 71% of involved lymph nodes. Neoadjuvant intra-arterial therapy with hormonal therapy yielded better survival rates than no intra-arterial therapy or our previous intra-arterial regimen.     

Successfully treated locally advanced breast cancer by intra-arterial infusion chemotherapy: a case report]

A 40-year-old female was admitted to our hospital with a large right breast tumor that was over 15 cm in diameter. We treated this locally advanced breast cancer by intra-arterial infusion chemotherapy. Through a catheter placed in the right subclavian artery, doses of 20-30 mg of ADM were injected intermittently with MMC and 5-FU. When a total of 120 mg of ADM had been infused, leukopenia developed, but this was immediately improved by G-CSF. With this treatment, her breast tumor and lung metastases were almost completely disappeared. Thus, an intra-arterial infusion chemotherapy was considered to be an effective treatment for locally advanced breast cancer.     

Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study

To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36 Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30 Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500 mg/m²/120 h was intravenously administered for 5 days (Days 1–5), and NDP at 120 mg/m²/6 h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert’s formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.     

Evaluation of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer. Of 405 patients undergoing colectomy in our department from July 1993 to February 2002, 38 had liver metastasis. We performed catheterization intra-operatively or postoperatively, and intra-arterial infusion chemotherapy was given for liver metastasis from colorectal cancer. Thirty-eight patients were treated with four different arterial infusion courses that mainly consisted of 5-FU. The 5-year survival rate was 8%. Maximal survival period was 68 months, and mean survival was 22 months. The effective rate was 20% Intra-arterial infusion chemotherapy was a useful treatment for liver metastasis from colorectal cancer. Resection of the liver metastasis was the first choice for operative liver metastases from colorectal cancer, and we performed intra-arterial infusion chemotherapy for patients postoperatively or patients with non-operative liver metastasis.     

A comparative study of intra-arterial infusion chemotherapy and systemic chemotherapy in the treatment of locally advanced breast cancer

A comparative randomized study of intra-arterial infusion chemotherapy (IA) and systemic chemotherapy (IV) was carried out on 41 patients with locally advanced breast cancer, and the following results were obtained. 1) The response rate of primary lesions to IA (63.2%) was better than that of IV (40.9%). 2) In the patients treated with IA, grade of leukopenia, as well as the percentage of gastro-intestinal disorders, was low. 3) More prolonged follow-up studies are required on the therapeutic effects on micrometastasis. The author confirmed that IA was an efficacious neoadjuvant therapy in terms of down staging of locally advanced breast cancer.     

Results of combined treatment of patients with locally advanced breast cancer

Eighty-seven women with previously untreated locally advanced, inoperable breast cancer were treated by induction chemotherapy combined with subsequent local and systemic treatment. Inflammatory breast cancer was diagnosed in 72 (87.7%) of these patients. In the remaining 15 patients, cancer of the breast in stage T3-4 N2b-3 according to the UICC classification was diagnosed. After remission induction, the patients were irradiated or operated upon. Maintenance chemotherapy was given after local treatment. The 3-year survival rate (61.5%) in the group of patients treated by surgery was significantly higher than the patients treated by irradiation (32.4%) or chemotherapy alone (12.5%). On this basis, a new program of treatment of locally advanced, inoperable breast cancer has been proposed.     

Local relapse after radiotherapy in locally advanced breast cancer patients

The study includes 99 patients with a locally advanced breast cancer. The mean age was 60.9±12.3 years, and 38.4% of the patients had a T₃ tumors and the remaining patients T₄ lesions. The most common histology was infiltrating ductal carcinoma, and in the 98% of the histologic samples the grade was moderate or high. All patients were treated with modified radical mastectomy, and radiotherapy. 37.4% of the patients received neoadjuvant chemotherapy. The radiotherapy schedule was 50.2%±1.6 Gy (1.8–2 Gy/day) with 1.25 MeV photons. Median follow-up is 4 years. The 5-year local-regional control probability, disease free survival and the distant disease free survival are 96.5%±3.9%, 61.4%±12.3% and 62.1%±12.3% respectively. The 4-year overall survival for patients with T₃ tumors was better than for T₄ lesions (85.8%±11.5% vs 68.5±13.1%) (p=0.18). In conclusion, the management of locally advanced breast cancer, should include surgery, radiotherapy and chemotherapy. The local control was excellent, and although patients die because distant disease they improve ed showed an survival.     

Role of ABCB1 and ABCC1 Gene Induction on Survival in Locally Advanced Breast Cancer

Abstract

Drug resistance to chemotherapy in patients with locally advanced breast cancer results in a decrease in treatment efficacy and in patient survival. This study aimed to evaluate the impact of ABCB1 and ABCC1 gene induction during chemotherapy on disease-free and overall survival of breast cancer patients.

Patients with locally advanced breast cancer were prospectively included. All patients were preoperatively treated with chemotherapy and underwent mastectomy. ABCB1 and ABCC1 gene and protein expressions were evaluated both before and after chemotherapy and investigated as molecular predictive parameters affecting disease free and overall survival. ABCB1 and ABCC1 gene expressions were evaluated with RTPCR following RNA isolation from tissue samples. P-glycoprotein and MRP1 in tissues were detected using immunohistochemistry.

Twenty-five female patients treated with either doxorubicin or epirubicin were included. Median follow-up time was 36 months during which 11 patients (44%) had recurrence, all of whom died. Mean disease-free survival for patients with and without ABCB1 gene induction was 13 and 55 months (p=0.0004), respectively, whereas overall survival was 21 and 57 months (p=0.0025), respectively. Mean disease-free survival for patients with and without ABCC1 gene induction was 32 and 48 months (p=0.97), respectively, and overall survival was 43 and 49 months (p=0.36), respectively.

ABCB1 gene induction decreases disease-free and overall survival in patients with locally advanced breast cancer due to anthracycline resistance. Detecting ABCB1 gene expression during chemotherapy helps to increase the efficacy of drug treatment by choosing the appropriate drugs resulting in prolonged survival.     

The Efficacy of Neoadjuvant Chemotherapy Compared to Postoperative Therapy in the Treatment of Locally Advanced Breast Cancer

The current approach to the treatment of locally advanced breast cancer is sequential chemotherapy, surgery and/or radiation, and consolidation chemotherapy. Although significant tumor response is seen with this regimen, there are few studies that compare this approach to postoperative chemotherapy. The purpose of this study was to compare the disease-free and overall survival of patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery to patients treated with surgery followed by adjuvant chemotherapy. Ninety-four patients with stage IIB, MA, and MB breast cancer were treated with a standardized chemotherapy regimen. The first group, 60 patients who were followed prospectively, was treated with neoadjuvant chemotherapy (NCT) consisting of vincristine, prednisone, Cytoxan, methotrexate, and 5-FU (CVFMP) followed by surgery and consolidation chemotherapy with adriamycin. The second group, 34 patients evaluated retrospectively, had surgery followed by postoperative chemotherapy (PCT) with CVFMP followed by adriamycin. Overall median follow-up was 38 months. In the NCT group, 45/60 (75%) patients had a clinical response to induction therapy and the median reduction in tumor size was 50%. The rates of local recurrence, distant recurrence, and death from disease were similar in the two groups. The time to local recurrence was similar for the two groups. However, the median time to distant recurrence was shorter in the NCT group (19 month vs. 31 months, p = NS). Overall median survival among the NCT patients was shorter than for the PCT group (30 vs. 47 months, p = NS). The current study suggests that postoperative therapy is comparable to a neoadjuvant regimen in patients with locally advanced breast cancer with regard to local recurrence, distant recurrence, and overall survival.     

The significance of neoadjuvant intra-arterial chemotherapy for locally advanced breast cancer by different methods]

For neoadjuvant intra-arterial (IA) chemotherapy in locally advanced breast cancer patients, Seldinger's methods were found to be convenient and had the same effect and outcome as conventional methods. The prognosis of the patients in whom IA chemotherapy was locally effective and had fewer than n 1 lymph node metastases was comparatively favorable. However, several patients who underwent IA chemotherapy later experienced local recurrence, and the cause of these patient's death was distant metastases in almost all cases. We recommend neoadjuvant IA and systemic chemotherapy, and systemic adjuvant chemotherapy.     

Intra-arterial chemotherapy with gemcitabine (GEM) for unresectable pancreatic cancer

PURPOSE: Most patients with pancreatic cancer are unresectable because of local invasion and liver metastasis at the time of diagnosis. To date, no treatment has had a significant impact on this disease. To deliver a high concentration of drug to the cancer, intra-arterial chemotherapy with GEM was performed in two patients with unresectable advanced cancer. PATIENTS AND METHODS: One patient, a 70-year-old man with liver metastasis, was treated with arterial infusion of GEM 1,000 mg/body. Another patient, a 55-year-old woman with local invasion and distant metastatic lymphadenopathy, was given intra-arterial infusion of GEM 400 mg and intra-venous infusion of GEM 1,000 mg/body. The patients were given GEM weekly for 3 weeks followed by a week of rest. RESULTS: In the first patient, the pain went away and CEA was decreased for 6 months. After that, the patient died due to intra-abdominal dissemination within 4 months. In the other patient, the pain went away. Tumor markers, such as CEA and CA19-9, were normalized and primary pancreatic cancer was reduced locally. The patient currently has a metastatic liver tumor, but she has had a significant improvement in performance status. CONCLUSION: Intra-arterial chemotherapy with GEM may be tolerated in patients with unresectable pancreatic cancer.     

保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床研究

目的 评价保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床疗效.方法 2003年4月～2006年12月,对35例浸润性膀胱癌患者采用经尿道膀胱肿瘤电切或膀胱部分切除术联合GC(吉西他滨 顺铂)方案动脉化疗治疗,总结分析肿瘤控制情况、膀胱保存率和患者的生存率.结果 33例患者获随访,2例失访,平均随访24.3个月(3～45个月).27例无瘤生存,2例带瘤生存,4例死于肿瘤转移,2年生存率为88.8%;19例无复发及转移,5例浅表性复发,3例浸润性复发,6例转移;25例保留膀胱生存,4例行挽救性全膀胱切除,4例死亡,2年膀胱保存率为74.1%.全部患者对动脉化疗耐受良好,无严重全身和局部不良反应.结论 保留膀胱手术联合GC方案动脉化疗治疗浸润性膀胱移行细胞癌近期疗效满意,毒副作用轻,值得临床进一步观察研究.     

Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer in a Malaysian Tertiary Hospital

Introduction: Neoadjuvant chemotherapy for locally advanced breast cancer is given with the aim of shrinkingthe disease sufficiently for surgery. However, many clinical trials investigating neoadjuvant chemotherapyregimens were conducted for operable breast cancer. Methods and Materials: Patients with T3-4, N2 M0 breastcancer diagnosed between January 2005 and December 2008 and who received at least one cycle of neoadjuvantchemotherapy were eligible for this study. Thirty-four patients were identified from the Chemotherapy DaycareRecords and their medical records were reviewed retrospectively. The neoadjuvant chemotherapy regimenadministered was at the discretion of the treating oncologist. Breast tumour size and nodal status was assessedat diagnosis, at each cycle and before surgery. Results: All 34 patients had invasive ductal cancer. The medianage was 52 years (range 27-69). 65% had T4 disease and 76% were clinically lymph node positive at diagnosis.The median size of the breast tumour at presentation was 80 mm (range 42-200 mm). Estrogen and progesteronereceptor positivity was seen in less than 40% and HER2 positivity, by immunohistochemistry, in 27%. Themajority (85%) of patients had anthracycline based chemotherapy, without taxanes. The overall response rate(clinical CR+PR) was 67.6% and pathological complete responses were apparent in two (5.9%). 17.6% ofpatients defaulted part of their planned treatment. Recurrent disease was seen in 44.1% and the median time torelapse was 11.3 months. The three year disease free and overall survival rates were 52.5% and 58% respectively.Conclusion: Neoadjuvant chemotherapy for locally advanced breast cancer in a Malaysian setting confersresponse and pCR rates comparable to published clinical trials. Patients undergoing neoadjuvant chemotherapyare at risk of defaulting part of their treatment and therefore their concerns need to be identified proactivelyand addressed in order to improve outcomes.