Monoclonal antibody treatment, which is one of the most promising molecular targeting cancer therapies, has recently become indispensable for the treatment of cancer due to its effectiveness and fewer side effects. Infusion reactions, which are similar to hypersensitivity or allergic reactions, are the generic term for the acute characteristic harmful reactions commonly associated with monoclonal antibody treatment. Those typically occur within the first 2 hours of the first infusion and are generally mild-to-moderate reactions which can be managed by either temporary interruption of infusion or administration of supportive care including corticosteroids, oxygen, or intravenous fluids. However, there are sometimes severe or life-threatening reactions, thus indicating the importance of closely observing the patient following the monoclonal antibody treatment. It is quite important that the entire medical staff understands the practical information regarding the timing and prevention or management of infusion reactions. In addition, it is also necessary to establish a system for prompt management of infusion reactions. Furthermore, sufficient information must be provided to the patient regarding infusion reactions.

There was limited knowledge about drug-induced ILD(DILD), when safety reports of acute ILD-type events in gefitinib-treated patients appeared in Japan. There is a need to better understand DILD including event incidence on different treatments and risk factors for developing DILD. Some studies using recent advances in imaging, molecular examination, and pathology are designed and conducted by an independent academic team to define the risk and increase understanding of ILD of various agents in a postmarketing surveillance. These studies may help to shed light on the underlying mechanisms of DILD and appropriate strategies for such events.

In cancer chemotherapy, serious complications including arterial and venous thrombosis and occlusion may occur, especially when bevacizumab(Bmab)is administered. Low-molecular weight heparin(LMWH)is recommended for the treatment of venous thrombosis in the guideline of Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer' by ASCO. Full-dose anticoagulation is reported to raise no risk of bleeding tendency. For a bowel perforation case, emergency operation may be required. In the treatment of such complications, wound healing delay due to Bmab administration has to be taken into account.

Advances in cancer chemotherapy, particularly development of molecular target therapies based on cancer biology, have significantly improved survival for cancer patients. Targeted therapies display generally favorable toxicity profiles, but reports of severe toxicities as seen with previous chemotherapeutic drugs have been increasing recently. Antineoplastic drug-induced central nervous system injuries sometimes progress to life-threatening complications. In this article, progressive multifocal leukoencephalopathy and reversible posterior leukoencephalopathy syndrome, which have been reported in association with targeted therapies, are reviewed clinically, etiologically based on reports in the literature. Treating physicians should be aware of the importance of early recognition and institution of appropriate management for these complications to reduce the risk of permanent neurological sequelae.

Anticancerdrug-induced cardiac toxicity has been recognized since the introduction and widespread use of the anthracycline derivative doxorubicin in the 1970's. Risk factors for cardiac toxicity have increased along with the development of multidisciplinary therapy, high-dose combination chemotherapy, and molecular-targeted therapy. Cardiac toxicity is now recognized as a common adverse effect. Cardiac toxicity as an adverse event caused by molecular targeted agents such as trastuzumab may lead to irreversible cardiac dysfunction. The developmental mechanism of cardiac toxicity has not been fully defined for any agent. At present, practical strategies include the evaluation of cardiac function before treatment and the monitoring of cardiac function during treatment to determine whether chemotherapy should be administered or withdrawn. Edema caused by molecular-targeted agents such as imatinib is considered a relatively new adverse event. Prompt and accurate differential diagnosis of edema is essential, followed by appropriate action. Currently, however, only symptomatic treatment is available. Future studies should attempt to elucidate the mechanisms of cardiac toxicity and edema associated with molecular-targeted agents, as well as develop new treatment strategies.

Targeted and biological therapies have been investigated as methods of improving anticancer therapy. One approach to targeted therapy is to inhibit tumor angiogenesis, which has a critical role in the development of cancer. However, the potential for further improvement in outcomes is likely to be limited by its nephrotoxic side effects such as urinary protein and hypertension. Among the anti-angiogenesis inhibitors, the humanized monoclonal antibody, bevacizumab, directed against VEGF(vascular endothelial growth factor), is the first anti-angiogenic agent to be approved for cancer therapy, but it has a high frequency of these side effects. Hypertension could be due to a reduction of eNOS activity and rarefaction of microvessels in various tissues and organs induced by VEGF inhibition. Bevacizumab also induces proteinuria, glomerular endothelial cell detachment and suppression of nephrin, an important protein for the maintenance of the glomerular slit diaphragm, sometimes leading to nephritic syndrome and/or thrombotic microangiopathy in the glomeruli. Periodic monitoring of blood pressure and urinary protein should be necessary in patients on anti- VEGF agents. Patients showing nephrotoxicities need special referral to nephrologists and to be treated using proper anti-hypertension drugs.

The cutaneous toxicities of epidermal growth factor receptor(EGFR)inhibitors including cetuximab, gefitinib and erlotinib, and multi-kinase inhibitors including imatinib mesylate, sorafenib, and sunitinib, are described. Acneiform eruption, paronychia and xerosis are common cutaneous toxicities in patients receiving EGFR inhibitors. Acneiform eruption usually consists of follicular papules and pustules without comedones and is observed in more than 50% patients. Paronychia occurs less frequently(10 approximately 15%)than acneiform eruption and involves multiple fingers and great toes. Xerosis is observed in 35% of patients. Painful fissures on the tips of fingers and toes can also develop because of excessive dry skin. Concerning multi-kinase inhibitors, pigmentary disorders and periorbital edema occur frequently during imatinib therapy, and hand foot skin reaction is observed by sorafenib or sunitinib. The hand foot skin reaction is clinically somewhat similar to acral erythema(hand foot syndrome)seen with docetaxel and other classic chemotherapy agents in that the lesions seem to be more discrete and hyperkeratotic. Subungual splinter hemorrhages have also been reported in 60% of patients receiving sorafenib and in 30% of patients receiving sunitinib. Although the mechanism of these cutaneous toxicities has not been fully elucidated, they are suspected to be caused by these molecularly targeted drugsc own actions. Therefore, the presence of these cutaneous toxicities may serve as a surrogate marker of treatment efficacy and a predictor of survival.

Great revolutionary changes have occurred in the diagnosis and treatment of gastrointestinal stromal tumor(GIST) due to the discovery and development of molecularly targeted therapy with imatinib and sunitinib, which have led to publication of several clinical guidelines for GIST. However, despite enhanced understanding of the clinical and molecular nature of GIST, there are many problems still remain. In this paper, I will focus on three GIST issues of great interest including: 1) laparoscopic surgery for GIST and gastrointestinal submucosal tumors; 2)multidisciplinary treatments for GIST, such as adjuvant therapy, neoadjuvant therapy, surgery during imatinib treatment, and surgery for focally imatinib-resistant GIST; and 3)the diagnosis and treatment of imatinib-resistant GIST.

We studied the prevention of phlebitis in 10 patients who had developed the symptoms after receiving vinorelbine to treat breast cancer at our outpatient chemotherapy clinic from July 2005 to August 2006. Veins proximal to the injection site were warmed using hot compresses during the vinorelbine injection and physiological saline was increased to wash out the drug after the injection from 250 mL to 500 mL in combination to investigate whether the treatment was effective in preventing phlebitis. The severity of phlebitis was significantly decreased after the combined treatment compared with the pre-treatment level (p=0.039). The combination was effective to relieve vascular pain during the injection in all 10 patients, and the number of event occurrences was significantly decreased (p<0.0005). It was also effective to decrease the frequency of vascular pain after patients returned home (p=0.001). The combination of hot compresses and increase of physiological saline for washing out was an effective treatment to prevent phlebitis caused by vinorelbine. The comparison of patient characteristics to find other contributing factors to phlebitis than vinorelbine revealed no association with the number of doses, diameter of the vein to be punctured, or pretreatment.

Although medical treatment for advanced renal cell carcinoma has included cytokine therapies such as interferon and interleukin-2, the treatment system has been revolutionized with the emergence of molecular target medicine. A vascular endothelial growth factor and its receptor for the target molecule are the mainstream, but the efficacy of inhibitors of an alternate pathway has been established. It seems that even newer molecular target medicine will be introduced in the future, but the optimal medicine based on the individual condition must be provided in renal cell carcinoma cases.

The treatment of metastatic colorectal cancer (mCRC) has developed significantly over the past 10 years. For nearly 40 years, the fluoropyrimidine 5-fluorouracil (5-FU) was the only active agent used for advanced metastatic disease. However, since the 1990s, the chemotherapy treatment options for patients with mCRC have been greatly facilitated with the introduction of several new cytotoxic agents. In particular, combination regimens that incorporate infusional schedules of 5-FU in combination with oxaliplatin (FOLFOX) and/or irinotecan (FOLFIRI) have significantly improved clinical efficacy as related to overall response rates, time to tumor progression, and median overall survival. More recently, monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab have become available for use in mCRC treatment in combination with cytotoxic agents and as monotherapies in Western countries. The addition of these target agents to the mCRC treatment armamentarium has resulted in more therapeutic options and improved treatment outcomes for patients. Currently, bevacizumab is the only target drug that is available for mCRC in Japan. In this article we review various treatment options, including cytotoxic and targeted agents, currently available for patients with mCRC in Japan and Western countries.

The efficacy and safety of reinduction therapy with gemtuzumab ozogamicin (GO)were investigated in 7 patients with relapsed or refractory CD33-positive acute myelogeneous leukemia. As the administration method, intravenous drip infusion of 9 mg/m(2) was conducted on day 1 and 15. Though CR was attained in 3 patients, the remaining 4 patients were assessed as PD. Grade 3-4 neutropenia and thrombopenia occurred in all patients, 4 of whom were complicated with febrile neutropenia and 1 with new pneumonia. On the other hand, except for grade 1 digestive symptoms and grade 1 GPT increase, none of the patients had serious complications. Though the treatment with GO is considered comparatively safe, sufficient supportive therapy as in the case of conventional chemotherapy is necessary against hematological toxicity. The effect of monotherapy with GO in reinduction is limited. It is necessary to appropriately select the cases and to investigate an effective administration method including the concomitant use of antitumor agent.

Capecitabine is one of the most effective oral regimens of chemotherapy against advanced or recurrent breast cancer. In addition, capecitabine could widely be used for treatment of colon cancer. It appears that more patients will be administered capecitabine because of its QOL benefits. However, Hand-Foot Syndrome(HFS)may appear to be about 50% of the patients who take this regimen. As a result, the patient's QOL is hindered and led to a reduction of the dosage or discontinuation of the treatment depending on the grade of adverse event. This time, we evaluated the efficacy of topical emollients, creams and vitamin B6 for prevention and reduction of HFS symptoms for patients who received capecitabine. We found the efficacy of preventative measures that the occurrence of HFS grade 1 or above could be decreased and delayed. We also noticed that these preventative measures appear to be decreased the occurrence of HFS grade 2 or above, which led to a reduction of dosage or discontinuation of the treatment. For continuation and completion of the treatment and securing of patient's QOL, the supportive measures are needed to control a variety of side effects, such as HFS and others, and a team care support is indispensable.

A 24-year-old man was admitted to the hospital for pancytopenia. Peripheral blood test and bone marrow aspiration demonstrated an increase in hypogranular promyelocytes. Karyotype analysis and RT-PCR showed 47, XY, t(15;17)(q22;q12), +12, and PML-RARA, respectively. The patient was diagnosed as having acute promyelocytic leukemia microgranular type (M3v) and was therefore administered all-trans retinoic acid (ATRA). Idarubicin and Ara-C were later added to the treatment regimen because of an increased number of leukemic cells. Nausea, vomiting and general fatigue associated with hypercalcemia developed on day 30. There were no findings indicating infection. The administration of ATRA was thus suspected to have induced hypercalcemia. ATRA was therefore discontinued and prednisolone and elcatonin were administered instead. Five days after this change, the serum calcium level normalized. Complete remission was thereafter confirmed on day 45. Hypercalcemia associated with ATRA therapy for APL is rare, and to date, there have been no case reports describing hypercalcemia associated with M3v in the literature. Interaction of fosfluconazole was suspected of causing hypercalcemia when used concomitantly with ATRA.

The decrease of the level of serum prostate specific antigen (PSA) after discontinuation of estramustine phosphate (EMP) has rarely been reported. We report 2 cases in whom EMP withdrawal syndrome was encountered. Case 1 was a 68-year-old man with a complaint of paresis of lower limbs. He was diagnosed with prostate cancer with multiple bone metastases. The serum PSA level was 9,300 ng/ml. He was treated with luteinizing hormone-releasing hormone agonist (LH-RHa) and bicalutamide (BCL). Six months later, EMP was started against PSA failure. During the 3-year treatment with EMP, PSA decreased to the nadir of 0.7 ng/ml and gradually increased to 14 ng/ml. After withdrawal of EMP, PSA decreased to 0.3 ng/ml (97.9% decline) and remained at this level for 4 months. Case 2 was a 61-year-old man who visited our hospital with gross hematuria. Transurethral bladder biopsy and transrectal prostate biopsy were performed. The diagnosis was moderately differentiated adenocarcinoma of the prostate that invaded to the bladder. Computed tomography (CT) showed a lymph node metastasis. He was treated with LH-RHa and BCL. The treatment was changed to EMP after PSA failure. EMP was withdrawn when PSA was 30 ng/ml. Then PSA decreased to less than 0.2 ng/ml (99% decline) and remained at this level for 9 months. We consider that in patients with EMP-resistant progression, EMP withdrawal syndrome should be checked.

This clinical trial was designed to evaluate the efficacy and safety of indisetron hydrochloride an oral 5-HT3 receptor antagonist, for the management of nausea/vomiting caused by chemotherapy for gynecologic cancer with paclitaxel/ carboplatin or docetaxel/carboplatin. Indisetron hydrochloride(8 mg)was administered orally to 46 gynecologic cancer patients at 0.5 hours before administration of the above chemotherapy agents. Number of patients who showed nausea or vomiting for 24 hours was counted. The complete vomiting inhibition rate at 24 hours after chemotherapy was 89.1%(41/46), and nausea inhibition rate was 71.7%(33/46). No serious adverse events were observed. These findings indicate that prophylactic administration of indisetron hydrochloride is safe and useful for inhibition of nausea/vomiting caused by cancer chemotherapy.