Intra-arterial infusion chemotherapy as an induction therapy in multidisciplinary treatment for locally advanced breast cancer. A long-term follow-up study

A multidisciplinary treatment including intra-arterial infusion chemotherapy as an induction therapy was administered to 55 patients with locally advanced breast cancer. Intra-arterial chemotherapy conducted preoperatively produced marked responses in primary and lymph node lesions with 78% complete + partial response (CR + PR), subsequently permitting extended radical mastectomy. Histologic examination of resected specimens also revealed that 33% 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 the 17 patients of historic control. Patients showing better local responses to intra-arterial chemotherapy had longer survival time with less frequent local recurrences. Intra-arterial chemotherapy is an effective modality for the treatment of locally advanced breast cancer.     

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.     

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.     

Retroperitoneal surgery in patients with nonseminomatous testicular cancer and minimal residual tumor

Optimal management of locally advanced breast cancer is controversial. Claims of superiority for neoadjuvant systemic therapy are based on comparisons with outdated historical control groups who received no chemotherapy. Between 1978 and 1987, 118 patients with locally advanced breast cancer underwent treatment and follow-up at the Medical College of Virginia. Median follow-up was 44 months (range 3-119 months). Actuarial 5-year survival for the entire group was 54%. This compares favorably with recent series using neoadjuvant chemotherapy in which 5-year survival rates of 40-65% have been reported. Primary tumor size larger than 9 cm, metastases to more than 50% of regional lymph nodes, and the presence of inflammatory disease were significant prognostic indicators. This series represents a contemporary control group of patients with locally advanced breast cancer in whom conventionally accepted guidelines for local and postoperative systemic adjuvant therapy were used. Until the optimal sequence of therapy is determined by prospective randomized trials, series such as this may serve as more appropriate controls to which the results of new therapies could be compared.     

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.     

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.     

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.     

局部晚期乳腺癌的治疗体会

目的：观察85例III期乳腺癌患者治疗的疗效,寻找提高疗效的策略。方法：2003年6月至2005年12月85例III期乳腺癌患者接受了外科手术治疗,根据是否接受新辅助化疗分为手术组（41例）和新辅助化疗组（44例）,比较两组的手术性质及治疗结果。结果：新辅助化疗组的无病生存期为59.1个月,明显高于手术组的43.1个月（P〈0.05）,新辅助化疗组的5年无病生存率为36.16%,手术组为34.14%（P〉0.05）。结论：局部晚期乳腺癌患者接受新辅助化疗后手术可提高无病生存时间,值得临床推广。     

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.     

局部晚期宫颈癌综合治疗方法探讨

目的 比较三种不同方法综合手术治疗局部晚期宫颈癌的优越性.方法 86例经病理证实的局部晚期宫颈癌,宫颈局部肿瘤直径>4 cm,Ⅰ b2期5例,Ⅱ a期39例,Ⅱb期39例,Ⅲa期3例.组织学分型:鳞状细胞癌72例,病理分级:高分化5例,中分化49例,低分化18例;腺癌14例.人院病人随机分为动脉化疗组(A)32例,根治性放疗组(B)27例,同步放化疗组(C)27例.结果 三种不同治疗方法术后淋巴结转移率分别是:A组:19.35%(6/31);B组:45%(9/20);C组:18.5%(5/27),经统计学处理,A组及C组相比无显著差异,C组与A组及B组相比,χ2值分别是3.86、4.61,P<0.05,差异有显著意义,手术切除率分别是96.9%、74%、100%,3年及5年生存率A组和C组相近,统计学上无显著差异,B组明显低于A组和C组,差异有显著意义.结论 动脉灌注化疗栓塞能明显提高局部晚期宫颈癌切除率,并不增加远期并发症,同步放化疗能明显提高近期疗效及5年生存率,年轻患者可优先选择动脉灌注化疗栓塞综合手术的治疗方案.     

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.     

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。     

Systemic chemotherapy does not increase the risk of gastrointestinal perforation.

BACKGROUND: Gastrointestinal perforation is a rare complication of gastric cancer. Although there is the perception of chemotherapy aggravating the perforation risk, the rate of perforation in patients with gastric cancer receiving chemotherapy is unknown. This study describes the incidence and clinical course of patients with gastric or gastroesophageal junction (GEJ) carcinoma who experience a perforation while receiving chemotherapy. PATIENTS AND METHODS: The records of patients with gastric or GEJ adenocarcinoma over a 6-year period who received chemotherapy for locally advanced or metastatic disease were reviewed. Extracted information included demographics, treatment received, and overall survival was calculated. RESULTS: 1032 patients at MSKCC received systemic cytotoxic chemotherapy for locally advanced or metastatic gastric or GEJ carcinoma; 11 patients experienced a perforation (1.1%, 95% CI 0.5-1.9%); 5/11 (45%) patients received further chemotherapy and had a median survival of 5.6 months. CONCLUSIONS: The rate of perforation in patients with advanced GEJ/gastric adenocarcinoma receiving chemotherapy is 1.1%, which is the same rate as in surgical series of patients presenting with perforation. Chemotherapy does not significantly add to the risk of gastrointestinal perforation.     

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.     

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.     

Preoperative therapy: recent findings

Preoperative systemic therapy (PST) is the standard treatment for locally advanced breast cancer and a standard option for primary operable breast cancer. PST for breast cancer is as effective as postoperative adjuvant therapy, which permits more lumpectomies and can be used to study breast cancer biology. For locally advanced breast cancer patients, the primary aim of PST is to improve surgical option. For operable breast cancer patients, the primary aim of PST is to obtain freedom from disease. Because of recent advances in treatment and our understanding of the disease, we summarized the current consensus on the adoption and benefits of PST, especially for operable breast cancer patients.     

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.     

Multimodality treatment of locally advanced breast cancer

From 1976 to 1985, 61 consecutive patients with locally advanced breast cancer were treated with multimodality therapy. Overall 5-year survival was 30% with a median survival of 36 months. 50% of patients relapsed within 13 months. Other factors such as menopausal status, side of illness (right or left breast), responses to systemic or to local treatment, survival and progression-free survival in responders and non-responders have been analyzed.     

Neoadjuvant Intra-arterial Chemotherapy in Locally Advanced Breast Cancer: A Prospective Randomized Study

A prospective randomized study of neoadjuvant chemotherapy wascarried out on 73 patients with locally advanced breast cancer.Group A (n 26) received no neoadjuvant therapy, group B (n 22)received intra-arterial infusions of epirubicin and group C(n 25) received intravenous epirubicin. The regression of theprimary tumor was significantly higher in group B than in groupC (68.2 vs 36.0%, P<0.05). The post-operative survival ofresponders to neoadjuvant therapy was better than that of non-responders.Side effects were milder in group B than in group C. There was,however, no difference among the three groups in terms of overalland disease-free survivals. Thus, neoadjuvant intra-arterialchemotherapy was effective for achieving loco-regional controlof locally advanced breast cancer with a low toxicity, but couldnot improve survival.     

Primary endocrine therapy in locally advanced breast cancers--the Nottingham experience

Introduction There are trials comparing different neoadjuvant chemotherapy regimens for locally advanced primary breast cancer (LAPC). Few studies have evaluated alternative therapeutic approaches towards LAPC. A previous trial from our institute in LAPC patients unselected for oestrogen receptor (ER) status, comparing primary endocrine therapy versus multimodal treatment, showed no difference in breast cancer related deaths or overall survival. We report our experience of primary endocrine therapy in ER+ LAPC. Methods Between 1988 and 2007, 195 ER+, non-inflammatory LAPC patients were treated with primary endocrine agents in our institute, due to patient choice, being unfit for chemotherapy, or recruitment into the above mentioned trial. All patients had disease assessable by UICC criteria. Results Median age was 69 years. The median follow-up was 61 months. 154 patients (79%) received endocrine treatment alone. 185 patients (95%) derived clinical benefit (complete response/ partial response/ stable disease) for ≥6 months from primary endocrine therapy. Overall 5-year survival was 76% and 5-year breast cancer specific survival was 86%. Conclusion In selected group of ER+ LAPC patients, primary endocrine treatment achieves excellent survival outcome and is a viable alternative to other modalities of treatment.