We report a prospective, single-arm, pilot study conducted by the Tokyo Metropolitan Oncology Group in order to evaluate the effect of a fish-oil enriched nutritional supplement(ProSureTM) during cancer chemotherapy in patients with advanced cancer. ProSureTM was given for more than 1 month to patients with advanced cancer whose prognosis was more than 3 months before enrollment. Laboratory data including serum albumin level, body weight, body composition, and functional status data were collected at baseline, 14 days, and 28 days. Oral supplementation consisted of 2 packs of ProSureTM per day for more than 28 days during chemotherapy. The study population included 50 patients. This study is now ongoing.

Monoclonal antibodies play important roles in medical oncology. The antibodies were designed as specific molecular targeting drugs and supposed to have less toxicity to normal cells compared to classical cytotoxic agents. Indeed, they do not have severe bone marrow suppression, nausea, or vomiting unlike cytotoxic drugs. On the other hand, clinicians often undergo characteristic adverse events we have never experienced before the appearance of the molecular targeting drugs. To fully utilize these powerful yet particular medicines, we have to be well aware of their severe or fatal adverse events and comprehend how to manage those toxic events. In this manuscript, important adverse events including infusion reaction, gastrointestinal perforation, cardiotoxicity, venous thromboembolism, and interstitial lung disease are subjects for discussion.

Temsirolimus is an inhibitor of mammalian target of rapamycin, with proven efficacy against advanced renal cell carcinoma (RCC), particularly poor risk and/or non-clear cell RCC, in a randomized first-line phase III trial. In this trial, adverse events (AEs)≥grade 3 occurred in 47.6% of patients treated with temsirolimus alone (n＝208), and the common AEs included asthenia, anemia and hyperglycemia. During the observation period of this trial, drug-related pneumonitis was detected ; 4 patients developed temsirolimus-related pneumonitis, including 2 with ≥grade 3. To date, there have not been any reports analyzing data from a large number of Japanese RCC patients treated with temsirolimus. However, judging from our experience, the severity as well as the frequency of AEs associated with temsirolimus in Japanese patients seem to be similar to those in the Western population. In this study, we summarize our clinical experience with the use of temsirolimus focusing on its AEs and try to clarify the characteristics of temsirolimus-related AEs in Japanese patients, and then present our data relevant to this point from our clinical studies in order to discuss the significance of the management of AEs encountered during treatment with temsirolimus.

Treatment with everolimus is known to prolong progression-free survival in patients with renal cell carcinoma resistant against tyrosine-kinase inhibitor therapy. The side effects must be known for more effective use of this drug. Information of side effects was collected from a randomized controlled study, the early post-marketing phase vigilance and from our own experience. Interstitial lung disease (ILD) was a potentially severe side effect. Incidence of ILD was relatively large compared with that of other target therapy agents. Infections, thrombocytopenia, stomatitis and others were experienced as other side effects. However, there were few uncontrollable side effects. Management of side effects of everolimus can be improved by obtaining sufficient knowledge.

Patients diagnosed with metastatic renal cell carcinoma (mRCC) are currently treated with oral tyrosine kinase inhibitors (TKIs). Sunitinib malate (Sutent R Pfizer INC) is an oral multitargeted TKI and is the mainstay of therapy for mRCC patients in Japan. Although it shows a high therapeutic response and prolonged survival rates, sunitinib exhibits a novel and distinct toxicity profile that requires appropriate monitoring and management. Therefore, the physician needs to understand the modalities to detect and cope with such adverse events to effectively treat the patient. We summarized the management of the most frequent and clinically significant adverse events of sunitinib treatment. Myelotoxicity, especially thrombocytopenia seemed to be the most common and severe toxicity (73% all grade, 36.8%, ≧grade 3). The incidences of thyroid dysfunction, fatigue, hypertension, hand-foot syndrome, nausea, diarrhea and oral changes were reviewed. The incidences of ≧grade 3 adverse events and dose reduction were higher than those in western reports. In our institution, fever was frequently observed (up to 63.1%). When the patient is at high risk of sunitinib assosicated adverse events, dose reduction from the beginning of sunitinib therapy may be useful. To maintain the patient's quality of life and for long-term administration of the sunitinib, it is worth while to modulate the sunitinib administration schedule for each patient.

Administration of more than 400 mg/day of sorafenib for 1 month prolonged progression-free survival (PFS) in Japanese patients with advanced renal cell carcinoma (RCC). This indicated that it is very important to prevent and manage side effects of sorafenib avoiding drug withdrawal or dose reduction. I mention the side effects of sorafenib and countermeasures in this review.

Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

With the aging of society, the number of elderly patients receiving chemotherapy has increased. Since organ function, particularly the liver and kidney function, is known to decrease with age, there is concern that severe side effects may develop in the elderly because of chemotherapy. It is a considerable challenge to establish safe, effective chemotherapy that enables elderly patients to maintain a favorable QOL. Therefore, we conducted a survey of the current status of chemotherapy side effects.