Ten cases of advanced and metastatic gastric cancer treated by weekly administration of paclitaxel were studied. The patients were 50-72 years of age, including 9 men and 1 woman. In this study, paclitaxel was administered by 1 hour intravenous infusion at a dose of 50-80 mg/m2 every week. Administration was continued for 3 weeks with 1 week rest. One to four cycles were performed at minimum. Paclitaxel was administered in 5 cases as 1st line treatment, 4 cases as 2nd line treatment and 1 case as 3rd line treatment. There were 2 partial responders and no complete responders, and the overall response rate was 20%. The response rate was 100% in liver, 100% in lung, 16% in lymphnodes, and 0% in peritonial dissemination. The clinical symptoms of pain and jaundice abated in one case, the size of the tumor decreased in one case, and a temporary decrease of ascites due to peritonial dissemination was seen in two cases. The level of tumor marker was decreased in 3 out of 10 cases. Side effects included grade 3/4 leukopenia in 10% of patients, and alopecia in 50%, but peripheral neuropathy was not observed. Weekly administration of paclitaxel appears to be well-tolerated and effective against advanced and metastatic gastric cancer.

Although hypersensitivity reactions to the anticancer drug are rare, since the reactions occasionally are clinical problems enough, that measure is important. The backgrounds (the etiologic mechanisms, the frequency, and etc) differ by each, therefore the knowledge for each medicine is required for measures including prediction and the prevention. This paper reviews the sensitivity reactions of various anticancer drugs (especially, paclitaxel, cisplatin and carboplatin) also including the molecular targeting drugs (trastuzumab, rituximab).

Cardiac toxicity due to anti-neoplastic agents has been recognized since doxorubicin, one of the most effective anthracyclines, was introduced in the early 1970s. Although the frequency of cardiac toxicity is relatively low compared with hematological and gastrointestinal toxicity, management of cardiac toxicity is crucial because of the possibility of irreversible cardiac damage. Recently, high dose-intense chemotherapy with G-CSF and stem cell transplantation, and mediastinal irradiation, produce even more toxic effects on the heart. This review describes some of the cardiac toxicity of anthracyclines and trastuzumab, and discusses attempts at management. The mainstay of management of cardiac toxicity is serial, adequate monitoring of cardiac functions.

Anti-tumor drugs often cause adverse reactions on both central and peripheral nervous systems. Prevention and early detection is essential, since proper treatment scarcely protects against adverse reactions once appeared in the nervous system. Precise neurological examination at bed side must be done before starting the chemotherapy and along the course periodically. Radiological diagnosis (including CT and MRI) and electrophysiological evaluation (including electroencephalogram and nerve conduction study) are informative as supplemental tools. Neurological and psychiatric symptoms and signs resulting from the major adverse reactions are reviewed, taken notice of prevention and countermeasures. Inclusive of amifostine there exist no neuroprotectants proving clinical utility at present. Some neuroprotectants are briefly introduced, of which efficacy animal experiments have demonstrated.

Patients who will receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs are not appropriate, and which drugs need dose modification. However, if the hepatic parenchymal abnormalities are caused by an underlying neoplasm and the neoplasm is sensitive to the drugs, it may not be necessary to reduce the dose. Clearly, this is an area where clinical judgment must be used to assess the risk/benefit ratio. Treatment of chronic hepatitis B virus (HBV) involves either the nucleoside analogue lamivudine or interferon alpha. The advantage of lamivudine includes limited adverse effects and the fact that histological improvement has been documented in the majority of patients. Primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HbsAg carriers. HbsAg screening is necessary before beginning chemotherapy for non Hodgkin's lymphoma patients. However, the main problem with long-term lamivudine therapy is the emergence of genotypic resistance because of base pair substitution at specific sites within the YMDD locus of the DNA polymerase gene. Significant hepatic dysfunction is uncommon among hepatitis C virus (HCV) infected patients treated with chemotherapy for hematological malignancies. However, infection with elevated AST levels is a significant risk factor for veno-occlusive disease after hematopoietic stem cell transplantation. Clinical judgment and a high index of suspicion remain critical tools in preventing and treating hepatic manifestations of cancer chemotherapy.

Chemotherapy-induced diarrhea is a well-documented side effect of many cancer treatments and is associated with increased morbidity and mortality. Chemotherapy-induced diarrhea negatively impacts patient quality of life and treatment outcome by requiring dose limitations or treatment interruption. The chemotherapeutic agent CPT-11 (irinotecan) has shown promising results as a single agent and in combination chemotherapy for the treatment of colorectal and small cell lung cancer. However, delayed onset diarrhea is considered to be its major dose-limiting toxicity. In some cases, it can be life threatening. To prevent CPT-11-induced delayed diarrhea, oral alkalization (OA) and control of defecation (CD) [Int J Cancer 92: 269-275, 2001] were developed based on fundamental studies [Int J Cancer 83: 491-496, 1999; Cancer Res 62: 179-187, 2002]. Oral administration of antibiotics [Cancer Res 56: 3752-3757, 1996; Clin Cancer Res 7: 1136-1141, 2001] or kampo medicine [Jpn J Cancer Res 86: 978-984, 1995; Jpn J Cancer Res 86: 985-989, 1995] to decrease beta-glucuronidase activity derived from bacteria in the large intestine was also reported to be successful in preventing delayed diarrhea. When CPT-11-induced delayed diarrhea occurs, the conventional treatment is loperamide [J Natl Cancer Inst 86: 446-449, 1994], and the early recognition and treatment of diarrhea with this opioid has reduced, although not entirely eliminated, patient morbidity. Other therapies are needed to treat patients with loperamide-refractory CPT-11 induced diarrhea, and the successful use of the somatostatin analogue octreotide has been reported [Support Care Cancer 9: 258-260, 2001; Ann Oncol 12: 227-229, 2001; Proc Am Soc Clin Oncol 21: 387a, 2002].

This report outlines measures for controlling nausea, vomiting, and anorexia caused by anticancer agents. Combination therapy with a 5-hydroxytryptamine (5-HT3) receptor antagonist and a steroid preparation is effective for controlling acute vomiting. In the chronic stage, however, the response to 5-HT3 receptor antagonists is less marked, so a steroid preparation is used as the major treatment in combination with a 5-HT3-receptor antagonist or metoclopramide. The antiemetic effect of recently developed tachykinin NK-1 (NK-1)-receptor antagonists has been shown to be additive to that of existing treatments for acute and chronic symptoms, especially chronic nausea/vomiting. Steroid preparations have been shown to improve anorexia, while medroxyprogesterone acetate (MPA: a synthetic progesterone) has been reported to improve anorexia and promote weight gain.

A 60-year-old woman (case 1) experienced severe pain in the lower part of her leg and sciatic nerve paralysis the following day after intra-arterial infusion of cisplatin for the treatment of uterine body cancer. The symptoms gradually improved in the next six months. The lesion was not detected on pelvic MRI after two months. A 49-year-old woman (case 2) complained of severe pain in the lower part of her leg three days after intra-arterial infusion of cisplatin for the treatment of uterocervical cancer. Enhancement of the right first sacral root was demonstrated by the pelvic MRI. The symptoms gradually improved with the symptomatic therapy. To our knowledge, this is the first report of lumbo-sacral radiculopathy associated with intra-arterial infusion of cisplatin presenting the enhanced lesion in the root on MRI. It was suggested that lumbo-sacral radiculopathy induced by intra-arterial infusion of cisplatin is not a rare complication and that MRI is useful in confirming the diagnosis. Various precautions should be undertaken to prevent such complications.

Second cancers induced by both alkylating agents and topoisomerase II inhibitors are reviewed with special reference to their distinct clinical features, incidences observed in the population at risk, cumulative risks, underlying molecular-genetic abnormalities, and also some detoxifying enzyme polymorphisms recently identified. Finally, it was discussed whether we can control these devastating diseases in the future.

Faced with limited resources and the desire to improve the quality of cancer care, there is an increasing interest among physicians in maximizing gains in cancer treatment. This paper discusses where to find cost-benefit estimates for a host of adverse events in cancer treatments. In order to clarify the relationship between the input resources and economic effects of supportive therapies against adverse events, we developed a system model, similar to the Marcov model, of prognosis of principal seven cancers and analyzed the balance of patient labor productivity (Benefit) and accumulated cancer care costs (Cost). Economic analysis is a useful guide to resource allocation and appropriate decision making for improving patient's QOL.

With the prolongation of life expectancy in Japan, cancer is increasing in the elderly. Several retrospective studies have shown that the frequency of toxicity, response to chemotherapy and overall survival are similar in elderly and younger patients with cancer with good performance status. However, because many investigators have arbitrarily excluded elderly patients from clinical trials and there have been a few clinical trials for elderly patients with cancer, no standard treatment in the elderly has been established for most cancer. New therapeutic strategies are clearly needed to prolong survival, and to improve quality of life in elderly patients with cancer.

It is difficult to find out optimal dose and schedule of anticancer agents. To reduce side effects of anticancer agents, there are several methods used: dose reduction, analogue development, utilizations of G-CSF or non-anticancer agent such as mesna for ifosfamide. Taxane agents such as paclitaxel and docetaxel, are widely used for the treatment of cancers of ovary, breast, lung, stomach, and head and neck. Dose-limiting toxicity of taxane is Grade 4 leucopenia with usual 24, 6, and 3-hour infusions. Efforts to reduce this toxicity were made, and one-hour weekly taxane infusion was found as safe and effective treatment, which is now widely used as single agent treatment or in combination. Development of paclitaxel one-hour weekly infusion was reviewed, as one example of reducing adverse reaction of leucopenia in this article.

At present, chemotherapy can seldom cure advanced gastrointestinal cancer. Low dose chemotherapy of regimen might be called palliative chemotherapy, but there has also been a growing interest in low dose chemotherapy as a means of reducing toxicity and improving responses. Several combinations such as low dose cisplatin (CDDP) + protracted infusional 5-fluorouracil(5-FU), leucoborin(IN) + 5-FU, weekly taxane and oral chemotherapy(TS-1) produce objective response in 30-50% of patients, and who get PR can actually enjoy improved QOL during the remission. Therefore, low dose chemotherapy for gastrointestinal cancer will be proposed aiming at some objective and/or subjective response with minimum toxicity to be alive as lons as possible.

Adverse skin reactions to anti-tumor agents, can be classified either as general symptoms or as local symptoms. The former type of symptom can manifest as intoxication dermatosis; however, while its occurrence is rare, the symptom that requires the closest attention is toxic epidermal necrolysis, the outcome of which is death in most patients. The latter type of symptom includes extravasation of anti-tumor agents and alopecia. Treatment of extravasation induced skin disorders includes prompt and repeated local injections of steroids, while treatment of alopecia includes scalp cooling and external therapies.

Lately, the focus of chemotherapy has become not only treating cancer but also maintaining patients' quality of life. Drugs used in chemotherapy can cause damage and toxicity in normal cells as well as cancer cells. The degree of damage could cause dose limiting toxicity and may become one of the reasons of cessation of chemotherapy. Neurotoxicity causes numbness of hands and legs which may continue to cause patients' suffering for a long time after the treatment. At present, the cause of neurotoxicity induced by chemotherapy is not clear, but it is urgent to prevent, identify and treat as early as possible. Methods for symptom management to relieve such patients' suffering needs to be developed as soon as possible.

Pulmonary toxicities, with special reference to interstitial pneumonia, due to cancer chemotherapy and/or chest irradiation were reviewed. Two sorts of mechanism of development of the interstitial pneumonia are considered; one is directly cytotoxic action to pneumocytes and/or pulmonary capillary endothelium and the other is an allergic mechanism against anticancer drug or its derivatives. The risk factors of cancer therapy induced interstitial pneumonia are an aged, poor performance status, and underlying interstitial pulmonary diseases. Recently some new serum markers involving KL-6 for interstitial pneumonia have been reported and further studies are needed to clarify whether these markers are predictive of subsequent pulmonary damage by anti-cancer treatments.

Cancer patients receiving chemotherapy have an increased risk of developing cardiovascular complications even if they have normal hearts, and the risk is greater if there is known history of heart disease. Various clinical cardiac complications that have been reported are arrhythmias, cardiomyopathy, vaso-occlusion or vasospasm resulting in angina or myocardial infarction. It is well know that cardiovascular complications in oncology patients is caused by anthracyclines. The trastuzumab as the new treatment option for the metastatic breast cancer may be associated with the development of a clinically significant cardiotoxicity. We described and reviewed the cardiotoxicity in oncology patients.