Outpatient chemotherapy for advanced lung cancer]

We reviewed the records of outpatient chemotherapy for advanced lung cancer in our institution. Thirty-two patients received 122 courses of cisplatin-free chemotherapy as outpatient treatments. Before outpatient treatment, every patient received the first chemotherapy as an inpatient treatment and the dose of cytotoxic drugs was reduced accordingly when side effects were judged to be untolerable. Only 1 patient needed hospitalization because of pneumonia with grade IV neutropenia. The overall response included partial responses (PR) 18%, no change (NC) 55%, progressive disease (PR) 11% and the median survival from the start of outpatient chemotherapy was 384 days. The monthly average cost of medical care per inpatient was more than three times as high as that of outpatients. Cisplatin-free chemotherapy for advanced lung cancer should be given as outpatient treatment not only to maintain the quality of life of patients, but also to restrain the total cost of medical care and to use hospital beds efficiently.     

Outpatient cancer chemotherapy employing implantable systems]

Outpatient cancer chemotherapy (OCC) employing implantable systems was introduced and the objects, conditions and problems of OCC were discussed based on experiences in 324 cases. The aims of OCC are improved QOL and the continuation of chemotherapy. Our requirements are safety, effectiveness, easy management and non-disturbance of activity. Implantable systems are very useful for OCC, especially continuous infusion combined with ambulatory pumps. However, the improvement of ambulatory pumps and the establishment of methods to evaluate OCC are required to further develop OCC.     

Maintenance chemotherapy for non-small-cell lung cancer

Currently, platinum-based combination chemotherapy is the standard first-line chemotherapy for non-small-cell lung cancer (NSCLC). Historically, platinum-based chemotherapy has been recommended for up to six cycles even for responders, and second-line chemotherapy has been considered when disease progression is confirmed. In spite of extensive investigations into maintenance chemotherapy, no positive data have been obtained; however, the results of recent clinical trials suggest both the safety and efficacy of maintenance chemotherapy in patients with NSCLC, although it is still controversial. In this review, we summarize the major clinical trials of maintenance chemotherapy in patients with NSCLC, and discuss its clinical validity and present future perspectives.     

Combination chemotherapy for advanced lung cancer

Lung cancer is now a major public health problem in Thailand. This study was undertaken to gain some preliminary data regarding the potential effectiveness in treating advanced non-small cell lung carcinoma (NSCLC) using an ifosfamide combination therapy IA(E)P. A clinical study was made of all 50 patients (Thais) with histologically proven, advanced NSCLC admitted to the University of Siriraj Hospital between 1985 and 1987 and followed up until February 1992. Survival was calculated for responders and non-responders as distinct groups, and for the different histological tumors among the responders. There were 22 cases of adenocarcinoma, 13 large cell carcinoma, and 15 squamous carcinoma. Twenty-seven out of 50 (54%) responded to treatment. The median survival of the response group was 17 months, compared with 5.5 months in the nonresponse group. The longest survival period was seen in patients with large cell carcinoma. The results suggest that moderate success might be expected in selected patients using the IA(E)P. Further work should be undertaken in developing countries using controlled clinical trials to more fully determine the efficacy of IA(E)P in treating NSCLC.     

Evidence based chemotherapy for lung cancer

There is often little foundation for decisions in experience-based or impression-based medicine. Therapy, however, should be based on the highest level of available evidence. In many clinical cancer practices, "uncertainty" exists. When no evidence is available, it is important that we perform clinical trials to generate new evidence. Organizing multi-institutional clinical trials in Japan is an urgent necessity. Limited disease SCLC Concurrent radiotherapy in combination with cisplatin and etoposide is considered to be a standard treatment in limited disease SCLC. Extensive disease SCLC Chemotherapy regiments such as PE or CAV/PE are standard therapy for ED SCLC. There is no current evidence for alternating chemotherapy, dose intensive chemotherapy, high dose chemotherapy, late intensification chemotherapy or maintenance chemotherapy in extensive disease SCLC. New drugs in combination with cisplatin have been reported to show promising antitumor activity in extensive disease SCLC. The impact of CPT-11 + CDDP on survival may be discussed at the 2000 ASCO meeting. Surgically unresectable stage III NSCLC In a recent meta-analysis, cisplatin-based chemotherapy plus radiotherapy was compared with radiotherapy alone in prolonging survival. Cisplatin-based chemotherapy with or followed by radiation was proven to enhance survival. However, the optimal sequencing of chemotherapy and radiation has not been definitively established. Chemoradiotherapy with new drugs (paclitaxel, docetaxel, vinorelbine, gemicitabine, CPT-11) has been evaluated for activity and efficacy. Metastatic stage IV NSCLC Compared with the best supportive care alone, cisplatin-based chemotherapy yields an absolute improvement in survival. New drugs in combination with cisplatin or carboplatin have been reported to show promising antitumor activity. There is no combination therapy including a new anti-cancer agent which can be recommended as a "gold standard". There is no current evidence that either confirms or refutes non-platinum-based combination chemotherapy. Second line chemotherapy Second line chemotherapy (docetaxel 75 mg/m2) improves survival in patients previously treated with platinum-based chemotherapy.     

Advances in chemotherapy for lung cancer

Combination therapy with platinum preparations still occupies a central position in chemotherapy for lung cancer. Third-generation regimens that combine an anticancer drug and a platinum preparation that were published in the 1990s remain standard therapy for untreated non-small-cell lung cancer today. Cisplatin or carboplatin is used as the platinum preparation, but combination therapy with cisplatin has been found to have a greater antitumor effect than combination therapy with carboplatin. However, there is very little difference between them, and on balance, when adverse reactions, etc. are taken into consideration, we do not think that it makes much difference which one of them is used. Clinical studies of combinations between platinum preparations and pemetrexed and S-1, which have been developed since 2000, have been conducted recently. Docetaxel has been established as standard therapy for recurrent cases, but based on the results of recent comparative studies, a survival-prolonging effect has been shown for pemetrexed and for EGFR tyrosine kinase inhibitors(gefitinib, erlotinib), which are molecularly targeted drugs, and it has now become possible to select treatment methods by choosing from a number of anticancer drugs. EGFR tyrosine kinase inhibitors have been demonstrated to have a very high cytoreductive effect on lung cancers that have EGFR gene mutations. The frequency of EGFR gene mutations is high in East Asia, including Japan, whereas it is very low in Western countries. Thus, the future course of development of chemotherapy for non-small-cell lung cancer may differ in Western countries and Asia, and the method of using EGFR tyrosine kinase inhibitors is expected to have great implications in Asia.     

Single-agent chemotherapy for non-small cell lung cancer

The survival and quality of life benefits of combination chemotherapy in patients with non-small cell lung cancer (NSCLC) are now well recognized. Since many clinical trials have been conducted in relatively young patients with good performance status, many elderly patients and patients with poor performance status are not offered chemotherapy because of concerns about higher risks of toxicity. The newer agents, including topotecan, are active as single agents in NSCLC, achieving response rates of up to 30%. Overall survival and symptoms may be improved when these agents are added to best supportive care. They are well tolerated in both elderly patients and patients with poor performance status. The major toxicity with the standard 5-day administration schedule of topotecan is myelosuppression, but weekly schedules may offer reduced toxicity while maintaining efficacy. Thus, single-agent therapy with newer agents is generally considered in elderly and poor performance status patients. However, combination chemotherapy may also be appropriate for some patients in these subgroups. Future studies of chemotherapy in NSCLC should not exclude elderly patients and patients with poor performance status.     

Critical pathways in chemotherapy for lung cancer

Differences of critical pathway in cancer chemotherapy from its protocol are the unification of the treatment, setting of the treatment goal and its provision for the patient. By the uniform treatment at least in the same hospital and the variance analysis of side effects with chemotherapy, the scientific and objective evaluation of treatment outcome and toxicities is possible. It is also useful for the consideration in the aspect of the ethics with the exhibition of the treatment by the provision of critical pathway for the patient. Therefore, critical pathway in chemotherapy for lung cancer is the useful tool to establish the clinical practice guidelines based on both scientific and ethical evidences in addition to the improvement of the patient satisfaction and the promotion of the team medical treatment.     

Cost-effectiveness of chemotherapy for nonsmall-cell lung cancer

After decades of research into its prevention and treatment, lung cancer remains the leading cause of cancer death in North America and Europe. Approximately 75% of all new lung cancer diagnoses are of the nonsmall-cell subtype, and less than 25% of these patients are potentially operable upon first detection. First-generation cisplatin-based chemotherapy regimens for patients with metastatic disease achieved a median survival of 175 days, with 15 to 20% of patients alive at 1 year.In recent years, vinorelbine, gemcitabine, paclitaxel, and docetaxel have emerged as promising agents in the treatment of advanced nonsmall-cell lung cancer. Evidence from randomized trials demonstrates that when these agents are combined with cisplatin, the objective tumor response is 25 to 40%, with a median overall survival approaching 300 days. In addition, recent studies have shown that single-agent docetaxel improves survival and quality of life in patients with platinum-refractory nonsmall-cell lung cancer. Since these modest but important improvements in the management of nonsmall-cell lung cancer are achieved at a significant cost, cost has emerged as a major consideration in health policy decision-making. This article reviews the pharmacoeconomic literature to provide guidance on the cost-effective use of chemotherapy in the treatment of advanced nonsmall-cell lung cancer.     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.     

Induction chemotherapy for resectable non-small-cell lung cancer

Lung cancer remains the leading cause of cancer death in American men and women. Non-small-cell lung cancer (NSCLC) accounts for 85% of these cases. Although surgery is the best curative approach for resectable NSCLC, long-term survival for patients with operable disease remains poor. More than half of patients who initially present with stage I to IIIA disease experience relapse of metastatic disease. Postoperative adjuvant therapy has been evaluated in several randomized trials, and provides a survival benefit. It appears reasonable to look to induction chemotherapy, or preoperative chemotherapy, to provide a similar improvement in survival with early treatment of micrometastatic disease. Multiple trials of induction therapy have been carried out with encouraging results. The use of various induction regimens with chemotherapy alone or chemotherapy combined with radiotherapy for stage IIIA NSCLC is under investigation. Randomized trials are under way to better define the role of induction therapy in the multimodality treatment of NSCLC.     

Adjuvant chemotherapy for resected non-small-cell lung cancer

Because of the high rate of distant disease recurrence, the 5-year survival of patients who have undergone complete surgical resection of localized non-small-cell lung cancer (NSCLC) is approximately 50%. Initial results from early studies of adjuvant postoperative chemotherapy reported an adverse effect of alkylating agent and older chemotherapy regimens on survival. Cisplatin-based combinations were the first to show a survival advantage. A 1995 meta-analysis of these studies suggested a 13% reduction in the hazard ratio for death (HR = 0.87), leading to a 5% survival benefit at 5 years. Still, these trials involved limited numbers of patients (N = 1,394), and the results failed to reach statistical significance (P = .08). Of the five largest subsequent randomized trials of platinum-based adjuvant therapy, three showed a significant survival advantage. Although it is impossible to determine the reasons for the differing outcomes of these studies, several key features distinguish them, and the data suggest that medically fit patients with resected stage IB or II NSCLC should be offered chemotherapy with a platinum/new drug combination.     

Second-line chemotherapy for non-small cell lung cancer

Several agents have been evaluated for the second-line treatment of patients with non-small cell lung cancer. The TAX 317 trial found that patients treated with docetaxel (Taxotere) 75 mg/m2 had significantly longer survival than those treated with best supportive care alone. In addition, symptom control was better for patients who received chemotherapy. The TAX 320 trial found that treatment with docetaxel 75 or 100 mg/m2 resulted in significantly higher response rates than treatment with vinorelbine (Navelbine) or ifosfamide (Mitoxana), and the 1-year survival rate was also significantly better for patients treated with docetaxel 75 mg/m2. A large randomized trial compared pemetrexed (LY-231514 or Alimta) 500 mg/m2 with docetaxel 75 mg/m2. Response and survival rates were similar in the two treatment arms, however, the toxicity profile of pemetrexed was superior to that of docetaxel with significantly less Grade 3/4 neutropenia and febrile neutropenia. Fewer patients in the pemetrexed arm required hospitalization. Topotecan (Hycamtin) 2.3 mg/m2/day orally for 5 days has been compared with docetaxel 75 mg/m2 in a large 800-patient study. The results of this trial are awaited. Gemcitabine (Gemzar) and irinotecan (Campto) have been evaluated both as single agents and in combination with each other and study results do not suggest that either of these drugs is superior to docetaxel or pemetrexed. The vinca alkaloid vinorelbine has proved to be inferior to docetaxel in a randomized trial. The epidermal growth factor receptor inhibitors gefitinib (ZD1839, Iressa) and erlotinib (CP-358774, OSI 774, Tarceva) have been evaluated in Phase II trials in the second- and third-line setting. Both drugs have demonstrated interesting response rates ranging from 10 to almost 20%. The results of placebo-controlled randomized trials of this family of drugs are awaited. In summary, several studies have now found a definite role for the second-line treatment of patients with non-small cell lung cancer.     

晚期非小细胞肺瘤的双途径化疗

目的研究不同的化疗方法治疗晚期非小细胞肺癌（NSCLC）并观察其疗效和毒副反应。方法将55例晚期NSCLC患者分4组,A组经皮肺穿刺瘤体内注射卡铂（PCI）+支气管动脉灌注（BAI）双途径化疗13例,B组PCI+VP-16静滴12例,C组单纯BAI18例,D组传统静脉化疗12例进行临床对比观察。结果近期有效率A组为76.9%,B组为58%高于C组33.3%,明显高于D组的16.7%（P<0.01）。一年生存率A组69.2%,B组75%,优于C组的38.9%,更明显优于D组8.3%（P<0.01）。一般状况的改善A、B、C三组明显优于D组（P<0.01）;而毒副反应均明显低于D组（P<0.01）。结论PCI是一种安全、简便的直接介入疗法,联合BAI或VP-16静滴双途径化疗是晚期NSCLC较为理想有效的综合性治疗手段,且PCI+VP-16疗法较PCI+BAI疗法更安全、简便、费用少,并发症少。     

Adjuvant chemotherapy for non-small cell lung cancer

Recently, several randomized trials with a large number of enrolled patients have shown that postoperative adjuvant treatment improves survival among patients with completely resected non-small cell lung cancer (NSCLC). Platinum-based chemotherapy has been reported to be effective for patients with postoperative stage I to IIIA NSCLC in western countries. On the other hand, uracil-tegafur was also shown to improve survival among patients with stage I adenocarcinoma in Japan. We reviewed the results of recent randomized trials and meta-analyses, and discuss the current role and problems related to adjuvant chemotherapy in NSCLC.     

Second-line chemotherapy for non-small cell lung cancer

Several agents have been evaluated for the second-line treatment of patients with non-small cell lung cancer. The TAX 317 trial found that patients treated with docetaxel (Taxotere^®) 75 mg/m² had significantly longer survival than those treated with best supportive care alone. In addition, symptom control was better for patients who received chemotherapy. The TAX 320 trial found that treatment with docetaxel 75or 100 mg/m²resulted in significantly higher response rates than treatment with vinorelbine (Navelbine^®) or ifosfamide (Mitoxana^®), and the 1-year survival rate was also significantly better for patients treated with docetaxel 75 mg/m². A large randomized trial compared pemetrexed (LY-231514 or Alimta^®) 500 mg/m² with docetaxel 75 mg/m². Response and survival rates were similar in the two treatment arms, however, the toxicity profile of pemetrexed was superior to that of docetaxel with significantly less Grade 3/4 neutropenia and febrile neutropenia. Fewer patients in the pemetrexed arm required hospitalization. Topotecan (Hycamtin^®) 2.3 mg/m²/day orally for 5 days has been compared with docetaxel 75 mg/m²in a large 800-patient study. The results of this trial are awaited. Gemcitabine (Gemzar^®) and irinotecan (Campto^®) have been evaluated both as single agents and in combination with each other and study results do not suggest that either of these drugs is superior to docetaxel or pemetrexed. The vinca alkaloid vinorelbine has proved to be inferior to docetaxel in a randomized trial. The epidermal growth factor receptor inhibitors gefitinib (ZD1839, Iressa^®) and erlotinib (CP-358774, OSI 774, Tarceva^®) have been evaluated in Phase II trials in the second- and third-line setting. Both drugs have demonstrated interesting response rates ranging from 10 to almost 20%. The results of placebo-controlled randomized trials of this family of drugs are awaited. In summary, several studies have now found a definite role for the second-line treatment of patients with non-small cell lung cancer.