Present and future evolution of advanced breast cancer therapy

Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents.     

Present and future in the surgical treatment of pancreatic cancer

Owing to the recent advances in surgical techniques and postoperative care, the operative indication for adenocarcinoma of the pancreas has been widened in Japan. In our institution, we have extended lymphatic and connective tissue clearance during surgical resection of this cancer. As a result, the 5-year survival rate has increased from 8% to 25% due to a significant decrease in the incidence of locoregional recurrence. The prognostic benefit gained by this procedure is seen mainly in those patients with stage III cancer or in whom no positive nodes were detected beyond the pancreatic head region. Thus, our extended surgery seems to have been useful due to eradicating the microinvasion in the peripancreatic connective tissues, rather than dissecting the positive lymph nodes. More advanced cancers should be treated by effectively combining chemo- and/or radiation-therapies with surgery. In order to cure the patients more easily with less-invasive surgery in the future, we should develop both an early diagnosis system and sensitive examinations of micrometastases or microinvasions.     

Systemic therapy for advanced pancreatic cancer

Death from pancreatic cancer remains high with few long-term survivors. Systemic chemotherapy with 5-fluorouracil-based combinations had minimal impact on natural history of this disease. Several new agents with activity against pancreatic cancer have been identified over the past decade. Gemcitabine has modest activity in this disease. Combination chemotherapy trials incorporating gemcitabine, cisplatin, 5-fluorouracil, oxaliplatin, docetaxel or irinotecan show improved outcomes in objective response rates and survival that need to be confirmed in prospectively randomized studies. Advancement in the understanding of the biology of pancreatic cancer has helped identify several molecular targets for the development of novel therapies. Ongoing and future treatment regimens for pancreatic cancer will incorporate traditional cytotoxic drugs and novel targeted therapies.     

Systemic therapy for advanced pancreatic cancer

Death from pancreatic cancer remains high with few long-term survivors. Systemic chemotherapy with 5-fluorouracil-based combinations had minimal impact on natural history of this disease. Several new agents with activity against pancreatic cancer have been identified over the past decade. Gemcitabine has modest activity in this disease. Combination chemotherapy trials incorporating gemcitabine, cisplatin, 5-fluorouracil, oxaliplatin, docetaxel or irinotecan show improved outcomes in objective response rates and survival that need to be confirmed in prospectively randomized studies. Advancement in the understanding of the biology of pancreatic cancer has helped identify several molecular targets for the development of novel therapies. Ongoing and future treatment regimens for pancreatic cancer will incorporate traditional cytotoxic drugs and novel targeted therapies.     

Surgery and drug therapy of advanced pancreatic cancer

By applying an en bloc resection of the pancreas with adjacent soft tissue, regional lymph nodes and pertinent vascular structures, a better prognosis could be made for patients with stages I or II carcinoma of the pancreas. The patients with stages III or IV of carcinoma of the pancreas could only be treated to a certain degree of effectiveness by using systemic combination chemotherapy with a very limited prognosis. Recent development of slow releasing anticancer agents would give more positive aspect for the management of persistent pains due to carcinoma of the pancreas with the absence of systemic side effect.     

Chemoradiation therapy for stage IV pancreatic cancer

BACKGROUND: Pancreatic cancer is a malignant tumor with a poor prognosis. It frequently presents with locally advanced and distant metastasis at the time of diagnosis. Favorable results were obtained by performing intraoperative radiation therapy (IORT) and chemotherapy (administration of GEM) for the treatment of inoperable pancreatic cancer. A study was conducted on its efficacy as an adjuvant therapy for inoperable and advanced pancreatic cancer. SUBJECTS AND METHODS: Between May 1998 and December 2002, 40 patients with stage IV pancreatic cancer were treated at our institution. The study comprised background factors, adjuvant therapy and survival rate. RESULTS: According to the treatment modality, the study population was classified into four groups: group A, consisting of 3 patients with localized unresectable tumors who had been treated with IORT: group B, 5 patients who underwent curative resection of primary tumor combined with IORT: group C, 6 patients who were administered GEM combined with IORT: group D, 26 patients not falling into groups A, B or C. The mean survival for group A, B, C and D was 10.3 months, 6.7 months, 16.8 months and 9.4 months, respectively. The 1-year survival rates were 0%, 0%, 80.0% and 19.3%, respectively. The mean survival and the 1-year survival rate were significantly better in group C than in the other groups. In group C, the tumor decreased in size, invasion of large vessels and pancreatic posterior evolution was suppressed, and 4 patients survived for 17 months or more. CONCLUSIONS: Prolongation of the survival period was shown by concomitant IORT and administration of GEM for inoperable advanced pancreatic cancer. Thus, attempting to combine chemotherapy with IORT and giving additional consideration to the administration method was shown to provide adjuvant therapy that can be expected to be effective against stage IV inoperable pancreatic cancer.     

晚期胰腺癌的内科治疗进展

胰腺癌是恶性程度极高、预后极差的消化系统肿瘤。由于发现时多为晚期,因此化疗、放疗、靶向等内科治疗是目前晚期胰腺癌的主要治疗手段。以吉西他滨、氟尿嘧啶、铂类为基础的传统化疗在晚期胰腺癌治疗中疗效有限,白蛋白结合型紫杉醇、厄洛替尼、尼妥珠单抗等药物尚处于临床试验阶段。因此,寻求新的靶标及治疗手段显得尤为重要。本文就晚期胰腺癌的内科治疗进展作一综述。     

Evolution of systemic therapy for advanced pancreatic cancer

The prognosis for advanced pancreatic cancer remains poor and successful drug development in this disease continues to be a major challenge. In the last decade the approach to drug development in pancreatic cancer has included a focus on combinations of cytotoxic agents. While some promising results were seen in Phase II studies, none of the Phase III trials of cytotoxic combinations were able to demonstrate an improvement in overall survival over that seen with the single-agent gemcitabine. Newer studies have assessed the efficacy of ‘targeted’ agents that inhibit pathways thought to be important in the development, growth, invasion and metastasis of pancreatic cancer. Although some agents had promising activity in preclinical studies, none has made a major impact in the clinic. There has been some success with the addition of the EGF receptor tyrosine kinase inhibitor erlotinib to gemcitabine, which was the first combination to achieve an overall survival benefit compared with gemcitabine alone in a Phase III trial. Future directions for drug development in pancreatic cancer will mainly involve testing new targeted agents, although some cytotoxic combinations are currently in Phase III testing. There is a need to better understand the biology of the disease and incorporate this into trials in an attempt to search for predictive and prognostic markers that will aid in drug development. Control of pancreatic cancer will require combinations of targeted agents, probably individualized based on tumor genetics. We are just beginning to explore the efficacy of combining targeted agents in the clinic.     

不可切除晚期胰腺癌的综合治疗

胰腺癌（Pancreatic cancer,PC）恶性度高,肿瘤生长迅速,是癌症死亡常见病因之一,在欧美国家排名第4位,我国排名第9位.尽管目前在诊断方面有所进展,但80％以上患者确诊时已为不可切除的局部晚期或转移患者,所以在治疗上必须接受多学科综合治疗,如化疗、放疗、靶向治疗等.本文就目前各学科治疗进展进行综述,以期为不可切除晚期PC的临床综合治疗提供参考和依据.     

晚期胰腺癌二线治疗的研究进展

一线使用吉西他滨已成为晚期胰腺癌治疗的标准方案,但是目前尚无标准的二线化疗方案。支持二线治疗优于最佳支持治疗的数据少之又少。我们总结已公布的二线化疗方案,大部分为Ⅱ期临床试验,以摘要的形式发表居多,没有单药的广泛研究。以药物的副作用作为代价,二线化疗的益处是非常有限的,但Ⅲ期随机试验还需要继续进行。未来的二线化疗将不仅以有效率或生存期作为评价,还将把临床受益率作为治疗目标。     

Current and future strategies for combined-modality therapy in pancreatic cancer

Treatment of pancreatic cancer remains a challenging task that often requires a multidisciplinary approach to confer optimal response and, ideally, maximize survival. A combination of locoregional approaches such as surgery and radiotherapy, along with systemic therapies for eradication of micrometastases, should be considered both for patients who are operative candidates and for those with locally advanced, unresectable disease. How best to combine these modalities in terms of schedule, timing, and choice of agents is a question that continues to be actively investigated. Some of these data are equivocal or conflicting; thus standards of care for combined-modality treatment have not been uniformly accepted to date. This article provides an overview of combined-modality therapy, focusing on the major studies that have guided our current approach to the treatment of pancreatic cancer and examining new strategies that are likely to improve outcomes and survival for patients in the future.     

Present conditions and future of ambulatory treatment and home care for breast cancer

Breast cancer is a disorder which occurs in the mammary gland, an organ on the body surface. Therefore, we traced the clinical course peculiar to breast cancer that is considerably different from lung and digestive cancer of a visceral origin. In addition, the standard treatment established worldwide for mammary cancer on the basis of cumulative of European and American evidence is in the surgery, internal medicine and radiologic fields. It is important that the is treated in an outpatient department setting and supported by home care. The construction of a team approach in medical care is an urgent issue for successful home care.     

Present and future of home anti-cancer chemotherapy for unresectable recurrence of colorectal cancer

Continuous hepatic arterial infusion chemotherapy (HAI) was performed for 100 colorectal cancer patients with unresectable liver metastases in our outpatient clinic. The administration schedule was 5-FU 250 mg/day for 7 days every other week. In this study, 93 cases were evaluable. The average dose of 5-FU was 24 g (3.0-66.5 g). The response rate was 59.1% (CR: 4 cases, PR: 51 cases, NC: 12 cases and PD: 26 cases). The prognostic outcome was significantly prolonged in the effective cases (50% survival duration was as follows: CR: 764 days, PR: 620 days, NC: 255 days and PD: 152 days). The complication rate with HAI was 15.1%, but nobody died from these complications. Hepatectomy after HAI was performed in 19 cases (20.4%) because of the effect of HAI. The three-year survival rate was 35.3% for HAI with hepatectomy and 3.8% for only HAI. There was statistically significant difference (p < 0.0001) between these two groups. Hepatectomy after HAI is a new strategy for unresectable liver metastasis of colorectal cancer. Recently, we performed home systemic chemotherapy using 5-FU for 3 recurrent patients of colorectal cancer and were able to continue this therapy safely for more than 2 months.     

晚期胰腺癌的分子治疗研究现状

胰腺癌是全球第七大致命的恶性肿瘤,分别是美国胃肠道恶性肿瘤和癌症相关死亡的第二大和第三大原因。与其他恶性肿瘤相比,晚期胰腺癌患者的生存率最低,中位总体生存率为2~8个月,5年生存率为8.5%。治疗十分困难,给临床医生带来极大挑战。目前晚期胰腺癌的治疗药物匮乏,化疗仍然是其主要治疗方法。虽然化疗能短暂的控制疾病的进展,但是在生存期的延长方面却差强人意。分子靶向治疗已在其他的瘤种中取得了里程碑般的成就,譬如肺癌、结直肠癌等,但晚期胰腺癌患者的分子靶向治疗效果并不显著。这需要我们去寻找新的治疗靶点和药物。本文基于胰腺癌信号传导通路及肿瘤微环境,总结和分析晚期胰腺癌分子治疗的研究现状,探索未来胰腺癌治疗的发展方向。     

Combined-modality therapy in pancreatic cancer: current status and future directions

The use of chemotherapy with concurrent radiation therapy remains a standard treatment option for patients with unresectable or resected adenocarcinoma of the pancreas. This treatment strategy is based in large part on data from serial Gastrointestinal Tumor Study Group (GITSG) trials, which have included 5-fluorouracil (5-FU). Unfortunately, the majority of patients continue to succumb to the disease process. Recently, there has been a resurgence in clinical trials investigating alternative combined modality treatment strategies for patients with pancreatic cancer. In this review, we will summarize both the mature and more recent data pertaining to combined modality therapy for patients with unresectable or resected pancreatic cancer. Strategies utilizing concurrent gemcitabine, alternative radiation therapy techniques, and/or altered sequencing of therapies will be highlighted. Such modifications to the approach in use since the 1980s will need to be fully considered as clinical trials utilizing chemoradiotherapy regimens and new systemic agents or novel targeted therapies are designed.     

Present status of home therapy cancer patients using an infusor

We started a department of medical oncology and the risk management system of cancer chemotherapy since April in 2004. After that, chemotherapy administration increased steadily in numbers, especially on an outpatient basis. For reliable venous access, we made active use of a central venous Port (more than 60% of cases) as a rout of administration. Fifty five patients with advanced colorectal cancer were treated by FOLFIRI or FOLFOX regimen from April 2005 to June 2006. Two hundred sixty four cycles of FOLFIRI and 276 cycles of FOLFOX were administered. One hundred sixteen cycles (44%) and 117 cycles (42%) were performed through home therapy, respectively. Twenty five out of 55 patients could shift to home therapy using an infusor. Nine out of 30 patients wanted to continue on an inpatient basis, because their private insurance for medical care did not support the outpatient chemotherapy.     

Chemotherapy for advanced pancreatic cancer: Past,present, and future

Advanced pancreatic cancer is a devastating illness characterized by significant morbidity and a brief median survival. Although standard chemotherapy with gemcitabine achieves only modest improvements in survival and quality of life, classic cytotoxic agents, such as 5-fluorouracil, pemetrexed, irinotecan, exatecan, cisplatin, or oxaliplatin, given alone or in combination with gemcitabine, have not proved superior. Thus, more recent trials have focused on targeting the biologic characteristics of pancreatic cancer. Although phase III trials of farnesyl transferase and matrix metalloproteinase inhibitors have not improved survival, encouraging preliminary results have been observed in phase II studies of inhibitors of the vascular endothelial growth factor and the epidermal growth factor receptor.     

Adjuvant therapy for pancreatic cancer: current status and future directions

This article summarizes the important past and ongoing adjuvant therapy trials for pancreatic cancer. The recent developments in the fields of radiosensitization, chemotherapy, and molecular-targeted therapy are outlined. Finally, the future study strategies for adjuvant therapy trials are discussed.