To elucidate the detailed profiles of major adverse events associated with gemcitabine hydrochloride, such as myelosuppression and interstitial pneumonitis (IP), we reanalyzed the results from Japanese clinical studies conducted by Eli Lilly Japan K. K. in patients with various types of cancer. Myelosuppression was clearly apparent after starting therapy at 2-3 weeks in the 28- day course monotherapy group, and at 2 weeks in the 21-day course combination therapy group with paclitaxel, cisplatin, or docetaxel. Increases in the number of courses did not necessarily lead to worsening of myelosuppression. IP possibly related to gemcitabine was seen in 6 out of 5 23 monotherapy patients and 5 out of 233 combination therapy patients. Five of these 11 patients were diagnosed in the first course; however, another patient was diagnosed with IP in Course 6. Two of these patients died of IP, one of whom had a past history of interstitial lung disease. These results indicate that ample attention should be paid to myelosuppression 2-3 weeks after the start of therapy, and to IP during the entire course of therapy.

Mucositis is one of the most frequent side effects induced by chemotherapy that damages the patients' QOL and response rate. The efficacy of Rebamipide and Polaprezinc mouthwash and uptake was evaluated. Nine patients who underwent chemotherapy and had some complaints related with mucositis were included as subjects. Rebamipide (300 mg) and Polaprezinc (150 mg) mouthwashing and uptake were performed by the subjects 4 times per day. Macroscopic examination and symptom research were performed until three months after beginning this medication. Macroscopic mucositis was shown in 5 patients previously and 4 patients improved. Seven patients had symptomatic improvement(p=0. 018). Rebamipide and Polaprezinc mouthwash and uptake is effective for patients who have mucositis induced by chemotherapy.

Thalidomide was approved in Japan for multiple myeloma treatment in October 2008. A program called the Thalidomide Education and Risk Management System (TERMS®) was established to help ensure that every effort is made to use the drug safely.

Combination therapy with S-1, superselective intra-arterial infusion of CBDCA and radiation therapy has been used to treat patients with oral cancer since 2005. In this study, the histopathological effects and toxicities following concurrent chemoradiotherapy were examined. The subjects consisted of 15 patients (10 men and 5 women) who were treated with S-1 (60-80 mg/day, 4 weeks), superselective intra-arterial infusion of CBDCA (300 mg/body) and radiation therapy (total dose 30-36 Gy) in our department from 2005 to 2009. Nine patients, showed T2 disease, 3 showed T3 disease, and another 3 showed T4 diseases. The primary cancer sites were the tongue (6 cases), buccal mucosa (4 cases), mandible gingival (3 cases), maxillary gingiva (1 case), and the floor of the mouth (1 case). The histopathological effects were evaluated according to Oboshi-Shimosato classification. Grade IV was shown in 10 cases (66. 7%), grade III in 1 case (6. 7%), II bin 3 cases (20. 0%), and II a in 1 case (6. 7%). All patients completed the treatment. The pathological response of the resected tumor was grade IIbor higher in 14 cases (93. 3%). While good histological effects were noted, there was one patient for whom viable tumor cells remained in the central part of the tumor. The present study indicates that further investigation is needed to determine the best dosing and dosing schedule.

We report a case of adriamycin-induced cardiomyopathy with severe functional mitral regurgitation and congestive heart failure (CHF). Mitral valve replacement (MVR) and papillary muscle approximation (PMA) were effective for this case. A 68-year-old man had adriamycin-induced cardiomyopathy and had required repetitive hospitalizations for CHF for the past 10 years. He also required additional CHF hospitalizations after implantation of a device to perform cardiac resynchronization therapy. His echocardiogram showed severe mitral regurgitation and reduced left ventricular function. We performed MVR and PMA for his functional mitral regurgitation. We preserved the tendinous cords of the anterior and posterior leaflets of the mitral valve. His echocardiogram showed improved left ventricular systolic function and reduced left ventricular volume. He has made satisfactory progress after the operation and he has not required further hospitalizations for CHF. MVR with preservation of bilateral tendinous cords and PMA are very effective procedures for functional mitral regurgitation and intractable cardiomyopathy.

We report the case of a 65-year-old woman with a delayed radiation ulcer and bleeding caused by bevacizumab. She has been undergoing chemotherapy for advanced colon cancer for two years. She received a mastectomy and adjuvant chemoradiotherapy for right breast cancer twenty-one years ago, and colon cancer with liver metastasis was detected using PET two years ago. Since last year she has been treated with bevacizumab chemotherapy bevacizumab due to increased liver metastases. As a result, her radiation ulcer worsened and bleeding occurred repeatedly. On suspicion of an adverse event, we stopped the bevacizumab, and that improved the radiation ulcer and the bleeding. In this case, we discussed radiation induced ulcers, wound healing, and adverse events caused by bevacizumab.

The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1 alone. We clinically analyzed 8 oral squamous cell carcinoma patients showing a complete response(CR)to chemotherapy with S-1 alone. These patients received chemotherapy consisting of 2 weeks' administration, including 5-days' administration and 2- days' termination, following a 1-week rest. Adverse effects were observed in 4 patients. However, all of them were grade 1 toxicities. The average length of S-1 administration before achieving CR was 9. 8 ± 3. 1 weeks(3. 3 ± 1. 0 courses). Seven patients had a recurrence. The prognosis of this group was 5 deaths by local recurrence, and 1 death by lymph node metastasis. The average length of disease progression was 447. 4 ± 479. 5 days. Two patients, one who received surgery and the other who received irradiation after chemotherapy by S-1, are alive without tumors. The 1-year and 3-year disease-free survival rates were 100% and 37. 5%, respectively.

To evaluate the feasibility of oral fluoropyrimidines after resection and microwave coagulation(MCT), or radiofrequency ablation(RFA)of liver metastases from colorectal cancer.

S-1 based therapy is a valued standard chemotherapy regimen for unresectable gastric cancer in Japan. S-1/ CDDP therapy has been highly effective, especially for patients under 75 years old who have good organ function. However, it is the elderly and/or patients with renal dysfunction who make up the majority of the candidates for chemotherapy in general hospitals. These factors make it difficult to apply the results of RCTs to chemotherapy regimens.

The risk management of interstitial pneumonitis in cancer chemotherapy not only involves an adverse event by an anticancer drug, but there are four steps with the incidence of interstitial pneumonitis: 1 ) the time before chemotherapy treatment, selection of chemotherapy regimens and patients, 2 ) the time chemotherapy treatment is performed, 3 ) the time during following-up, 4 ) the time when interstitial pneumonitis occurs. It is necessary to decrease the risk of interstitial pneumonitis by several steps, cooperating with an entire medical staff.

Myelosuppression is one of the most serious adverse effects induced by chemotherapy targeting solid tumors and hematological malignancies, and results in neutropenia, anemia and thrombocytopenia. In particular, prompt and appropriate treatments are required for febrile neutropenia, because that disease may be fatal.

Chemotherapy-induced peripheral neuropathy(CIPN)is one of chemotherapy's common and disabling adverse effects. It may be caused by many chemotherapeutic agents including the taxanes(paclitaxel, docetaxel), the vinca alkaloids(vincristine, vinorelbine, vinblastine), the platinum analogues(cisplatin, carboplatin, oxaliplatin), bortezomib and thalidomide, among others. Once the symptoms have developed, they may lead to compromising patients' quality of life(QOL). For medical oncologists, the management of CIPN remains an important challenge. At the present time, no agent has shown enough solid beneficial evidence to be recommended for the treatment or/prophylaxis of CIPN. The standard of care for CIPN includes awareness and early detection of neuropathy, and dose reduction and/or discontinuation of the problematic agents.

It has been suggested that skin symptoms may cause psychological distress associated with change in appearance, and affect patients' quality of life(QOL). Also, there is a correlation between the severity of skin disorder resulting from treatment with epidermal growth factor receptor(EGFR)inhibitors(cetuximab, panitumumab, erlotinib)and their clinical effects. Treatment with EGFR inhibitors needs to be continued as long as possible while treatment-related skin symptoms are managed appropriately. Adherence to this approach will benefit the patients. Daily self-skin care(keeping the skin surface clean, maintaining moisture retention, and preventing irritation)is the most important countermeasure for hand-foot syndrome resulting from oral administration of fluorinated pyrimidine anticancer drugs(capecitabine, S-1). An early introduction of effective countermeasures including dose reduction/establishment in the rest period is essential for management of such syndrome.

Chemotherapy-induced mucositis is a clinically important and sometimes dose-limiting toxicity of cancer treatment, including standard-dose chemotherapy, high-dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis.

Patients who receive ambulatory-based chemotherapy worry about nausea and vomiting leading to appetite loss, decreased activity, and finally, the lowering of QOL. The management of nausea and vomiting also prevents decreased body weight loss, encourages compliance with chemotherapy treatments, and promotes social activity. Recently, NCCN, ASCO, MASCC as well as JSCO guideline for antiemesis were updated and approved for delayed antiemetic drugs in Japan. According to these guidelines, we should administer antiemetic drugs appropriately to prevent anticipatory emesis. Last year, in a retrospective analysis of head and neck cancer, in a comparison of before and after the use of aprepitant, the use can improved the dose intensity of CDDP and one-year survival after chemotherapy. We need to have prospective analyses, but appropriate use of antiemetic drugs and management of chemotherapy lead to a better clinical outcome and safety.

Infusion reactions and allergic reactions are common side effects of anti-cancer drugs, and are known as hypersensitivity reactions. Patients with these severe reactions require close attention because these reactions sometimes lead to critical conditions. Infusion reactions are caused by cytokine release, although the precise mechanisms involved are still obscure. Infusion reactions are often caused by rituximab, an anti-CD20 antibody, and other monoclonal antibodies. Allergic reactions, mediated by IgE, are observed with a variety of chemotherapeutic drugs, especially platinum compounds and taxanes. An acute severe allergic reaction is called anaphylaxis, and is often fatal unless treated appropriately. In this review, we describe the prevention of hypersensitivity reactions and their treatment based on our clinical experience.

Extravasation of chemotherapeutic agents can potentially cause severe skin damage such as ulceration, resulting in a dramatic decrease in quality of life in patients receiving chemotherapy. Although guidelines for treating extravasation were published in Japan a few years ago, practical procedures on how to deal with it, have not been presented in the guidelines yet due to a lack of supporting evidence. Therefore, each hospital should provide its own procedures to manage the extravasation of chemotherapeutic agents. We describe here the treatment of extravasation by topical injection of steroids. We have never experienced significant skin damage in patients after treatment with topical steroid injections.

The patient was a 70-year-old woman. She was admitted to our hospital complaining of fever and dyspnea. Chest CT scan showed a 50 x 30-mm tumorous shadow in S6 of the left lung and honeycomb lung in both lower lobes. As the result of cytodiagnosis with ultrasonic echo, adenocarcinoma was diagnosed. Clinical stage was IIIA (T3N2M0). We selected carboplatin and paclitaxel with bevacizumab as first-line chemotherapy, but at 7 days after the initiating it, the chest X-ray showed left pneumothorax. A chest drainage tube was placed in the left thoracic cavity. The patient was treated repeatedly pleurodesis with minocycline and OK-432. The pneumothorax required 3 weeks to cure. We selected carboplatin and paclitaxel without bevacizumab for the second course, and the pneumothorax did not recur. Pneumothorax was a serious adverse event associated with bevacizumab-containing chemotherapy. It is necessary to be aware of the possibility of pneumothorax when we treat lung adenocarcinoma with bevacizumab-containing chemotherapy.