Our outpatient cases for home anti-cancer chemotherapy using a CV port and a portable pump system

We report our outpatient cases for home anti-cancer chemotherapy using a CV port and a portable pump system. A total of 119 patients with advanced and recurrent cancer were performed at an outpatient clinic or provided home anti-cancer chemotherapy since December 1996 until December 2005. Of these patients, 18 patients were provided home anti-cancer chemotherapy using a CV port and a portable pump system (5 with gastric, 4 colonic, 2 rectal, 1 lung, 1 hepatic, 1 duodenal, 2 breast, and 2 pancreatic). Fifteen patients had died, and 3 patients are alive and undergoing continuous therapy. The response revealed 3 cases with partial response, 13 cases with no change and 2 cases with progressive disease. No severe side effects were seen, and no troubles of catheter and port were experienced as well. Not only the treatment of outpatients for home anti-cancer chemotherapy was effective and maintained the patient's QOL, but also contributed to a marked decrease of medical costs compared to admission therapy.     

The prospects of the outpatient clinic or home anti-cancer chemotherapy for unresectable recurrence of colorectal cancer

In this study, we analyzed the effectiveness of anti-cancer chemotherapy at the outpatient clinic. We administered CDDP 5 mg/day every 5 days for a week with continuous systemic chemotherapy by 5-FU 500 mg/day for 3 weeks in the hospital, and in the outpatient clinic CDDP 5 mg/day every two days for a week with UFT 300 mg/day orally every day to 145 patients with unresectable recurrence of colorectal cancer. The 50% survival duration after beginning of this chemotherapy was 310.0 days. One-year and 2-year survival rates were 44.4% and 11.7%. One hundred and nine cases were evaluated. The total response rate was 19.3%, and the highest response rate was seen in metastatic lymph nodes (37.5%). The mean duration of continuation of this chemotherapy and the mean duration of staying at home was 188.2 days and 237.8 days. The mean rate of home stays was 68.6%. The group of performance status (PS) 0 or improving PS, accounted for 74.5% of all cases. The occurrence rate of adverse effects was as follows; stomatitis: 17.9%, diarrhea: 11.7% and bone marrow suppression: 13.1%. However, the occurrence rate for cases of grade 3 or 4 was only 1-4%. According to these results, this was an excellent chemotherapy to maintain the patient's QOL from the outpatient clinic.     

The future of chemotherapy at home--from outpatient chemotherapy to chemotherapy at home

Chemotherapy for colorectal cancer has changed greatly. A continuous systemic chemotherapy like FOLFOX or FOLFIRI became a standard. It is necessary to get sufficient knowledge and technique of chemotherapy for an infusion port system and a portable pump system. The risk management aspect is very important. Both strict and steady drug mixing and an administration system are necessary. It is also important to make a 24-hour surveillance system for any unusual conditions. The hospital as a whole must come to grips with these problems. The chemotherapy at an outpatient clinic or home will become a standard in the near future because it preserves the patients' QOL.     

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.     

Loco-regional chemotherapy at the outpatient clinic for gastric cancer patients with home enteral nutrition

In over the 10 years from 2000-2010, 21 gastric cancer patients received loco-regional chemotherapy with home enteral nutrition (HEN) at an outpatient clinic because of insufficient oral intake. These loco-regional chemotherapy regimens consisted of 5 intra-aortic chemotherapies, 4 hepato-arterial infusions and 12 intra-peritoneal chemotherapies. Five out of 8 cases that had measurable lesions showed PR, and 3 cases revealed PD. The patients received HEN with peptide central formula, 400-1,200 kcal/day in night time. The average duration of HEN was 12.9 months. The post-operative nutritional management was needed for continuation and securing of outpatient chemotherapy. The author reported an experience of the outpatient loco-regional chemotherapy with HEN for the gastric cancer patients who could not eat a sufficient volume of food.     

Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.     

Trial of outpatient anti-cancer chemotherapy with infusion of 5-FU and cisplatin for advanced gastric and colorectal cancers

We carried out a pilot study on the clinical efficacy and safety of outpatient anti-cancer chemotherapy with 5-FU and CDDP for 5 patients with advanced cancer of the stomach or colon, using two disposable balloon pumps. The protocol was combined chemotherapy with continuous intravenous infusion of 5-FU (500 mg/body/day) and CDDP (10 mg/body/day) in 5-day courses for 1 week, and the therapy was repeated as long as possible. Pharmacokinetic study showed that the mean serum concentration of 5-FU was 64.3+/-9.2 ng/ml, and the serum concentration of total Pt increased continuously during CDDP injection. Thus, both drugs were injected, safely and surely. One patient had a clinically evaluable lesion, and the anti-tumor effect of this case was SD. But the serum CEA level was decreased in 3 cases. The side effect of Grade 3 and 4 was not seen, but nausea, vomiting, anorexia, and weight loss were observed frequently. This therapy enabled the patients to stay home 51.6+/-10.0 days longer than with the usual methods in hospital, and this therapy was thought to improve their quality of life. Thus, this therapy is feasible and quite useful, but much attention must be paid to the patient's oral uptake during the therapy, and the clinical effects should be evaluated in randomized control trials.     

Preoperative chemotherapy and anti-cancer effect of gastric carcinoma

For the purpose of the study of macroscopical and histopathological anti-cancer effects, preoperative cancer chemotherapy was performed in 31 cases with gastric carcinoma. Gastric carcinoma with preoperative chemotherapy showed advanced cancer in 15 cases, and early cancer in 16 cases. During preoperative chemotherapy, the drug 5-Fu or 5'-DFUR was administered orally. The results were as follows; i) Macroscopical change of early cancer cases with anti-cancer chemotherapy showed the onset and healing of ulceration in the cancerous lesion and the change of granular pattern in the IIc floor. ii) Early cancer cases had a multi-centric histopathological anti-cancer effect which showed regenerative epithelium in the cancerous lesion. iii) The extent of the histopathological anti-cancer effect in advanced carcinoma showed greater in the deep layer of cancer invasion. Consequently, morphological changes of early cancer cases with chemotherapy are similar to the cases without chemotherapy. The onset of cancer damage in advanced carcinoma is in the cancer invasive zone, deep layer.     

New anti-cancer agents--from cytotoxic systemic chemotherapy to target-based agents

Lung cancer is the leading cause of cancer-related death throughout the world including Japan. During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. To date, clinical research has defined the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) as modern platinum-based doublets considered more efficacious than any single regimen and with no added benefit to triplet therapies. However, we have reached an efficacy plateau with these agents. Rearrangement of the drug combination or change of the drug doses and schedules will not result in significant further progress. New, less toxic agents that improve survival and quality of life are clearly needed. In the last three decades, we have gained a growing understanding of the molecular biologic changes and the complex series of cellular signals that allow cancer cells to manifest behavior. This provides an opportunity to develop novel therapies aimed at inhibiting some of these changes and signals. Targeted agents, primarily the epidermal growth factor receptor inhibitors, have led to a new era in the treatment of NSCLC. This paper will review the current status of cytotoxic agents and molecular targeted therapy in lung cancer potential useful in the treatment of the patients.     

The development of an outpatient treatment system for cancer chemotherapy

It is necessary to develop a system of treatment to provide cancer chemotherapy on an outpatient basis. Facilities needed include treatment service sites, outpatient laboratories, and chemotherapy pharmacies where safety cabinets are available. Medical oncologists, chemotherapy nurses and pharmacists should conduct cancer chemotherapy after obtaining informed consent from the patient. Chemotherapy protocols, ordering systems and risk management for medical errors must also be established in the agreement to perform chemotherapy. The problems encountered in the experiences at the Outpatient Treatment Service of National Cancer Center Hospital East are discussed.     

Effects of combination chemotherapy of MCNU with various anti-cancer agents

Combination chemotherapy using the water-soluble nitrosourea MCNU with various anti-cancer agents was studied using L1210 leukemia and P388 leukemia. In titration experiments MCNU showed remarkable antitumor effects at doses from 5 mg/kg to 80 mg/kg, producing numbers of 60-day survivors with L1210 leukemia. In L1210 leukemia, respective combinations of MCNU with the antimetabolites, MTX, 6-MP, 6-TG, MCNU, 5-FU and Cyclo-C showed enhanced antitumor effects. MCNU combined with each of ADR, MMC and CPM also showed marked anti-tumor effects with 60-day survivors. In P388 leukemia MCNU combined with each of ADR, MMC, VDS and CPM produced strong anti-tumor effects with numbers of 60-day survivors. In the results of these combinations, especially the combinations of MCNU + 5-FU in L1210 leukemia and MCNU + CPM in both L1210 and P388 leukemia, a significant increase in mean survival time was achieved. These combinations also produced many 60-day survivors which were considered to be due to the synergistic antitumor effects of the combined drugs.     

Central venous access port-related complications in outpatient chemotherapy for colorectal cancer

BACKGROUND: The current standard chemotherapy for advanced or metastatic colorectal cancer in Japan is FOLFOX or FOLFIRI therapy. Although both therapies include continuous infusion of 5-fluorouracil (5-FU), outpatient home chemotherapy is possible by placing a central venous access port (CV-port) and using a portable disposable pump. The port system has been placed more frequently since the approval of FOLFOX. Consequently, more complications involving ports and pumps have been encountered. METHODS: At our hospital, 232 patients with colorectal cancer underwent outpatient home chemotherapy by placing a CV-port and using a portable disposable pump for continuous infusion of 5-FU between 1998 and 2005. Incidence and contents of complications involving ports and pumps were investigated retrospectively. RESULTS: A total of 54 incidents of complications involving ports and pumps were identified in 3142 treatments (1.72%) from among 34 of the 232 patients (14.7%). In 2005, when FOLFOX was introduced, 31 incidents occurred in 1903 treatments (1.63%) for 19 of 149 patients (12.8%). Incidents involved port placement (n = 6), catheter and port system-related complications (n = 15), puncture needle-related complications (n = 3), skin complications related to tape fixation (n = 20) and pump-related complications (n = 10). In 10 patients (4.3%), system-related complications made therapy difficult to continue and system exchange was required. CONCLUSIONS: Technical troubles involving ports and pumps occurred at a certain rate, and skin incision was required for system exchange in some cases. When performing outpatient chemotherapy using ports and pumps, thorough prior guidance and double-checking must be implemented, and proper countermeasures must be established.     

A trial of outpatient chemotherapy for recurrent head and neck tumors

A four-drug combination chemotherapy (bleomycin-methotrexate-vinblastine-CCNU) had been used in 38 evaluable patients with recurrent squamous cell carcinoma of the head and neck region on an outpatient basis. A large number of these patients had carcinoma of the oral cavity (45% of total). Nineteen patients (50%) responded to this regimen with a greater than or equal to 50% regression of their measured tumors. The median survival of all patients was 34 weeks. There was one chemotherapy-related death and the overall toxicity was mild. This convenient regimen can be considered a useful alternative to more aggressive therapy.     

Economic impact of outpatient chemotherapy in multiple myeloma

The development of alternatives to hospitalisation is mandatory in cancer patients. A retrospective analysis compared the costs relative to two modalities of administration of VAD chemotherapy (hospital versus outpatient) in multiple myeloma. This study was carried out from the perspective of the French health care system, including direct hospital and ambulatory costs. The robustness of results was tested in a sensitivity analysis. Forty four patients were included: 27 in the "hospitalisation" arm and 17 in the "outpatient" arm. Among the cycles planned to be administered in outpatient, only 5 cycles (4 patients) have to be administered in hospital. The length of hospitalisation was consequently reduced with outpatient administration (-11.2 days) and it induced a significant cost saving as 3,066 euros (-32%) per patient. In sensitivity analysis, this cost saving varied from 1,282 to 3,667 euros. Our study showed the safety and the economic interest of outpatient administration of VAD chemotherapy in multiple myeloma. Facilities and training are required to develop ambulatory chemotherapy.     

Patient-included multi-disciplinary team approach in the outpatient chemotherapy

To reassure safety and comfort in providing cancer chemotherapy on outpatient basis, patients and medical staff must form a team to manage the treatment together. Many patients tend to receive treatment rather passively in Japan until now, thus intervention is necessary for such patients to undergo the treatments with better understanding of the possible treatment side effects as well as the ways to deal with them. As for the risk management and/or symptom management, it is important to encourage patients to improve their ability for self care and to heighten their awareness that they can indeed take part in their own management. Also, when specialist intervention is required, consultation must be sought immediately so that the problem can be resolved promptly. It is important for the patient and the medical staff to share the same goal to provide safe and comfortable treatment, and for the member of the team fulfilling their respective specialist roles toward that goal.     

A comparison of human G-Csf and human Gm-Csf given concurrently with anti-cancer chemotherapy

Granulocyte-colony-stimulating factor (G-Csf) and granulocyte-macrophagecolony-stimulating factor (GM-Csf) were each given concurrently with continuous infusion of doxorubicin, ifosphamide, or vinorelbine. Both cytokines enabled the dose intensity of these three anti-tumor agents to be substantially increased without an increase in drug toxicity. The effect of Gm-Csf as a stimulant of dendritic cell production and function was noted.     

The cooperation between pharmacists and nurses in outpatient cancer chemotherapy

The cooperation between each section and exchange of information are important in outpatient cancer chemotherapy. At Tokai University Hachioji hospital, we adopted a sheet that supports aseptic preparation of anticancer agents and a sheet for exchanging information. The purpose of the sheet is to grasp the information that we get in each section. The main information that we exchanged was its contents about an order input, drip infusion rate and a dosage order of antiemetic or anticancer drugs. By having added the sheet, we could unify a mixture preparation and show a clear presentation to nursing of a preparation method that can be enabled. In addition, acquisition of information obtained in each of the section became easy. In this way, by cooperating between sections and sharing information that we obtain, it is thought that it leads to improving the safety of outpatient cancer chemotherapy.     

Intraarterial infusion chemotherapy for metastatic liver tumors using multiple anti-cancer agents suspended in a lipid contrast medium

An ethiodized oil, Lipiodol (Lipiodol Ultra-Fluid, Laboratoire Guerbet, Paris, France), when injected into the hepatic artery, is selectively retained by liver tumors. Thus, anti-cancer agents suspended in Lipiodol can be delivered specifically to liver tumors. Before clinical trials of this new drug delivery system were begun, the movements of drugs suspended in Lipiodol were examined in vitro. It was found that 5-fluorouracil, doxorubicin, and mitomycin C were continuously released from oil phase to water phase, and when these three drugs were collectively suspended in Lipiodol, each was released independently. During clinical investigations, 42 patients with unresectable metastatic liver tumors were treated with intraarterial infusions of anti-cancer drugs in Lipiodol. As a result, the administration of a combination of anti-cancer agents suspended in Lipiodol was shown to be effective in controlling metastatic liver tumors. It was concluded that such a method could be applied to a variety of metastatic liver tumors with different drug sensitivities.     

米托蒽醌联合方案治疗非何杰金淋巴瘤的临床观察

观察两组含米托蒽醌联合方案对８９例非何杰金淋巴瘤的疗效。方法；用ＭｘＣＯＭＢＰ及ＭｘＣＯＭＰ两组方案治疗各期ＮＨＬ，计算ＣＲ率，有效率，Ｘ＾２及Ｐ值，并以来来判断两组方案的优越性。结果：８９例患者的ＣＲ率为５３．９％，有效率为８６．５％，Ⅰ＋Ⅱ期患者的疗铲明显优于Ⅲ＋Ⅳ期患者；ＭｘＣＯＭＢＰ方案的有效率９３．８％优于ＭｘＣＯＭＰ方案的有效率７８．１％，对Ⅲ，Ⅳ期及高度恶性患者效果更佳。