It is important to diagnose infectious events in cancer patients during chemotherapy. Since many of them have complications of febrile neutropenia (FN), determining its cause is critical for their treatment course. We analyzed all febrile events (>38.0 degrees C, single axillary temperature) in hospitalized cancer patients treated at Shizuoka Cancer Center over a period of 8 months. Based on the clinical presentation at the onset, we estimated the cause of fever and classified it as infection, tumor fever, immunologic reaction or unknown. Clinical presentations found at the onset of FN were categorized into 4 groups: (1) oral mucositis, and (2) respiratory, (3) gastrointestinal and (4) cutaneous findings. We detected 85 febrile episodes (median age 58, range 26 approximately 86; 37 males and 48 females). Neutropenia was observed (500/mL) in 52. 9% (45/85) of the patients and clinical symptoms were detected in 74.1% (63/85). In eleven of 18 infection-proven cases, we successfully predicted the infection focus at the onset of fever. Multivariate analysis revealed that initial high fever, antimicrobial prophylaxis, cutaneous findings and severe neutropenia were important influencing factors in predicting infectious disease during FN. Physical examination can support the diagnosis of the cause of fever in FN patients.

Cetuximab and panitumumab, both anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAb), have demonstrated clinical activity in patients with colorectal cancer. They are well tolerated, but they involve various adverse events that are rare among cytotoxic agents. Typical adverse events associated with anti-EGFR MAbs include infusion reaction, skin toxicity, lung toxicity, and hypomagnesemia. It is necessary to recognize and manage adverse events promptly to continue treatments without drug discontinuation. This report details the adverse events and their management with anti-EGFR MAbs use.

A 59-year-old man was diagnosed with IgA-kappa multiple myeloma in October 2005. He was treated with 4 courses of VAD and autologous peripheral blood stem cell transplantation (auto-PBSCT) after 200 mg/m(2) melphalan in September 2006, followed by a second auto-PBSCT after 200 mg/m(2) melphalan in February 2007. However, he did not achieve a very good partial response (VGPR). Laboratory examinations showed increased serum IgA level and renal dysfunction gradually progressed. Bortezomib was then started at a dose of 1.3 mg/m(2) in November 2008. After three cycles of bortezomib, the patient developed numbness, pain and weakness of his upper and lower extremities. The sensation of position and vibration was diminished in the fingers and toes. He developed left foot drop and gait disturbance due to left peroneal nerve palsy. Autonomic dysfunction such as orthostatic hypotension and urinary retention also occurred. Nerve conduction studies showed severe sensorimotor polyneuropathy particularly in the lower extremities. He developed grade 4 motor neuropathy and severe painful neuralgia. Six months after the cessation of bortezomib, these symptoms gradually improved and he was able to walk with support and discharged. Close monitoring of neurological symptoms and prompt dose-reduction or cessation of bortezomib are important to prevent the progression of irreversible peripheral neuropathy.

Patients with cancers such as breast or prostate cancer who have been treated with hormone deprivation therapies or anti-cancer agents for certain periods of time frequently manifest reduced bone mass or pathological fractures during their clinical course. These are likely due to an imbalance between osteoblastic bone formation and osteoclastic bone resorption resulting from hypogonadism. Bone should be carefully monitored in cancer patients who are going to continually receive adjuvant hormonal or anti-cancer therapies. Administration of anti-bone resorption agents such as bisphosphonates may be necessary to maintain bone mineral density and protect pathological fractures in these cancer patients.

Recent development of effective regimen on the cancer chemotherapy and the improved management for the side effects of chemotherapy will give a safety management for outpatients with cancer. The chemotherapy for outpatients will produce their prolonged and better life at home and improve their quality of life. In the ambulatory center for the chemotherapy at Tokai University Oiso Hospital, the role of the pharmacists is important for the safety and comfortable management of patients. At first, pharmacists check each regimen of the cancer chemotherapy, and give the patients the information of expected side effects of the chemotherapy. Moreover, a special medical record for each patient is important on the safety management, especially for the communication of other medical staffs.

We report the successful desensitization of a patient with a hypersensitivity reaction to carboplatin. A 54-year-old woman with advanced ovarian cancer went into remission after 10 courses of paclitaxel plus carboplatin (TC). After 7 months, cancer recurred in the vaginal cuff, and surgery was performed. Cancer recurred again in the vaginal cuff 6 months later, and she was administered TC. A hypersensitivity reaction attributed to carboplatin occurred during the third and fourth courses, and the drug was withdrawn. Because the initial response to TC was good, we decided to attempt desensitization to carboplatin. The desensitization procedure was successful, and the patient subsequently tolerated four additional courses of TC, with no further signs or symptoms of hypersensitivity. A complete response was achieved. A carboplatin desensitization regimen may allow patients with platinum-sensitive ovarian cancer to continue to benefit from therapy.

Here, we report a case of extensive osteonecrosis of the maxilla associated with a history of bisphosphonate (BP) therapy for management of bone metastases from breast cancer. A 66-year-old woman was referred to our hospital because of a fistulation on the right side of the maxilla in May 2005 by her dentist. The patient had a medical history of breast cancer with bone metastasis that was treated by chemotherapy with 45 mg pamidronate in 2 weekly courses for 16 months. We suspected that this rare case of osteonecrosis was caused by chemotherapy with BPs. Palliative treatments, including antibiotic therapy and local irrigation, were administered. Finally, extensive osteonecrosis of the maxilla occurred.

We analyzed 127 consecutive patients who received trastuzumab-based chemotherapy from December, 2003 to February, 2009 in our hospital. Of 127 patients, cardiac dysfunction appeared in 6 patients(4. 7%). Cardiac dysfunction was defined as a decline in left ventricular (LV) ejection fraction (EF) < or =55% with absolute reduction of at least 10% from baseline. Among the 6 patients with cardiac dysfunction, one patient suffered symptomatic heart failure. Other patients were asymptomatic. The 4 patients of the 5 patients recovered their cardiac dysfunction after withdrawal of trastuzumab. Patients with trastuzumab-associated cardiac dysfunction had a history of administration of epirubicin or taxane, lower registration LVEF, and larger LV end-diastolic dimension (> or =49 mm). We recommend that LV function be assessed by echocardiography or multigated radionuclide angiography scans prior to instituting trastuzumab therapy and at three-month intervals during therapy. Trastuzumab should be discontinued in patients who develop a decrease in LVEF below 45% or congestive heart failure.

We evaluated clinical factors associated with concurrent chemoradiotherapy (CRT) toxicity and efficacy in resectable locoregionally advanced squamous cell carcinoma of the head and neck. Subject were 115 subjects with stage III or IV carcinoma undergooing 58 to 70 Gy of irradiation (median total dose: 66 Gy) concurrently with 2 cycles of chemotherapy of 5FU at 1000 mg/m2, 120-hour continuous infusion and cisplatin at 60 mg/m2. Grade 3 to 4 mucositits differed significantly between 13% in N0 and 59% in N1 to 2. No significant difference in planned therapy completion was seen between 87% in N0 and 82% in N1 to 2. Three-year overall survival (OS) was 66% and progression-free survival (PFS) 55%, in median follow-up of 42 months (range: 5.8 to 91 months). OS differed significantly between 86% in stage III and 57% in IV, 78% in T0 to 2 and 62% in T3 to 4, 83% in N0 to 1 and 53% in N2, 77% in adjuvant chemotherapy (nedaplatin plus UFT) and 50% in no adjuvant chemotherapy, and 33% in the tongue and 77% in the oropharynx. PFS significantly differed between 72% in T0 to 2 and 49% in T3 to 4, 77% in CR and 53% in PR, and 22% in the tongue and 58% in the hypopharynx, 66% in the oropharynx, and 53% in the larynx. Multivariable analysis showed strongly independent risk factors associated with OS and PFS to be advanced T and N stage, no adjuvant chemotherapy, and the tongue as the site. CRT was effective in treating resectable locoregionally advanced squamous cell carcinoma of the head and neck. It is possible that adjuvant chemotherapy will improve CRT OS and PFS. Other additional treatment will be needed, however, to improve OS and PFS in cases having a dismal diagnosis such as tongue cancer.

We conducted a multicenter postmarketing study to investigate the efficacy and safety of reinduction therapy with a high-dose cytarabine-containing regimen for pediatric patients with relapsed or refractory acute leukemia. Seven of 13 patients (53.8%) with ALL achieved complete or partial remission, and only 1 of 6 patients (16.7%) with AML achieved partial remission. The frequent non-hematologic adverse events were gastrointestinal toxicities, such as vomiting, diarrhea and abdominal pain, as well as pyrexia and headache. Infection appeared in 9 of 20 (45%) patients. There were two death during reinduction therapy. One died of invasive bronchopulmonary aspergillosis, and the other died of intracranial hemorrhage and renal failure. These results indicated that a high-dose cytarabine regimen is effective as reinduction therapy in pediatric patients with relapsed ALL, and supportive care is essential to prevent or control treatment-related adverse events, such as infection.

A 61-year-old woman with an unresectable malignant rectal stricture underwent placement of an expandable metallic stent under endoscopic guidance. The stent was successfully implanted and her bowel obstruction was relieved. After treatment with bevacizumab for unresectable rectal cancer, she was admitted to our hospital because of rectal perforation. This case suggests that placement of a metallic stent in colorectal cancer cases may increase the risk of bowel perforation during bevacizumab-based chemotherapy.

Thirty-seven patients with advanced or recurrent colorectal cancer were treated with mFOLFOX6 or mFOLFOX6 with a Bevacizumab regimen between September 2008 and March 2009. Then, we evaluated persistent neuropathy using the National Cancer Institute Common Terminology Criteria for Adverse Events (ver. 3). As a result of the research, grade 1-3 sensory neuropathy was observed in 5.6% after 3 cycles, 44. 4% after 5 cycles, 83. 3% after 8 cycles, and 83. 4% after 10 cycles. The average dose of L-OHP (mg/m2) until persistent sensory neuropathy appeared was grade 1: 399.7+/-157. 0 (17/ 37 patients); grade 2: 418.0+/-214. 1 (5/37 patients); and grade 3: 498.0+/-152. 8 (3/37 patients). As has been shown in international clinical trials, the severity and frequency of L-OHP-induced neurotoxicity are associated with the cumulative dose and duration of L-OHP administration. Further research is necessary to develop strategies for preventing or treating this side effect.

A 66-year-old woman with small-cell lung cancer was administered chemo-radiotherapy consisting of cisplatin (CDDP) and etoposide (ETP). From day 3, she developed vomiting and hyponatremia that persisted despite fluid infusion and cortico-steroid administration. On day 7, the hyponatremia worsened (serum sodium level, 109 mEq/L), leading to disturbed consciousness and convulsions. The serum sodium level gradually increased after intravenous administration of hypertonic saline; on day 22, the serum sodium level was almost normal without any neurological implication. We diagnosed this clinical condition as renal salt-wasting syndrome (RSWS) on the basis of dehydration and high urinary sodium excretion at the onset. In the second course of chemotherapy, CDDP was replaced with carboplatin (CBDCA); consequently, hyponatremia was not observed. Hyponatremia that develops after the administration of CDDP may be due to not only the syndrome of inappropriate secretion of anti diuretic hormone (SIADH) but also RSWS. When RSWS is suspected, hypertonic saline should be administered.

A 58-year-old female presented with massive splenomegaly, leukocytosis and anemia. Bone marrow appearance was consistent with CML-AP, and t (9;22) (q34;q11) was detected on karyotyping. 600 mg daily imatinib mesylate (imatinib) was started and achieved complete hematological remission. However, pancytopenia was evident. Despite dose reduction and subsequent drug withdrawal, the pancytopenia worsened and she became transfusion dependent. Grade 4 pancytopenia persisted for 8 months after discontinuing imatinib. Bone marrow biopsy showed severe bone marrow aplasia with no morphological evidence of disease progression. Karyotyping showed minor cytogenetic response with no clonal evolution. Signs of hematological recovery appeared 8 months after stopping imatinib. The patient was re-started on imatinib at a dose of 100 mg/day. The dose was increased to 200 mg/day without hematological toxicity. Complete cytogenetic response (CCyR) was achieved 5 months after the re-administration of imatinib. The patient maintained CCyR with 200 mg of imatinib per day. Prolonged severe bone marrow aplasia has rarely been reported as a complication of imatinib therapy. This case also suggests that low-dose imatinib would be tolerable and effective for some CML patients who are intolerant of a standard dose of imatinib.

TS-1 is an oral anti-tumor drug, which contains 5-chloro-2, 4-dihydroxypyridine (CDHP), a compound mainly excreted in urine. Since the CDHP concentration is increased among patients with impaired renal function, the frequency of side effects of TS-1 increases in such patients. Therefore, we constructed a computer-aided system that enables prompt monitoring of creatinine clearance (Ccr) calculated from the serum creatinine levels of patients prescribed TS-1 at the time pharmacists prepare the medicine. With this system, we found two cases who were prescribed TS-1, despite their decreased Ccr. One was a patient whose estimated Ccr was less than 30 mL/min/m2. With such renal malfunction, pharmacokinetics of the drug was considerably changed compared with normal control, and the dosage should be reduced. The other case presented with severe jaundice and had only a mild decrease of renal function (Ccr: 50 mL/min/m2). So we measured the concentration of uracil in the urine and performed a drug lymphocyte stimulation test for further investigation of concomitant affecting factors. Our system is useful because it can show pharmacists both the dosage TS-1 patients take and their renal function at a glance in real time. This system can be adapted for every medicine which might accumulate in patients with renal dysfunction.

When methotrexate (MTX) salvage chemotherapy is performed for primary brain malignant lymphoma, use of leucovonrin rescue must often be extended due to delays in the degradation of blood concentration. We examined whether delay in MTX blood concentration degradation could be prevented by chai-ling-tang (Sairei-to) which has diuretic action. In the five cases examined were MTX blood concentration 72 hours after MTX administration was more than 1 x 10(-7) M. A single dose of 3 g of chai-ling-tang was administered three times on the day the MTX salvage chemotherapy was subsequently performed. MTX blood concentration at 72 hours post MTX administration and subsequent chai-ling-tang administration was less than 1 x 10(-7) M in all five cases. In addition, urea nitrogen and creatinine levels in serum increased and creatinine clearance decreased following MTX administration, however these changes induced by MTX administration were reduced by chai-ling-tang administration. Chai-ling-tang was effective in preventing an MTX deferent delay in MTX high-dose therapy by improving renal blood flow.

Accumulating evidences have shown that thiazolidinediones (TZDs), PPARgamma ligands, could exert anti-cancer actions in several human cancer cells. TZDs are capable to inducing growth inhibition, apoptosis and inhibition of cell invasion, thereby leading to their anti-cancer effects. The growth inhibition was mediated by a cyclin-dependent kinase inhibitor, p27(Kip1), accumulation which is induced by both inhibition of ubiquitylation of p27(Kip1) and reduction of degradation activity of p27(Kip1) by proteasome. In addition, a recent clinical observation has showed a 33% reduction in lung cancer risk among TZD users who have diabetes mellitus compared with nonusers, strongly suggesting TZDs possess clinically relevant actions. These results suggest that TZDs may be novel agents to treat malignant tumor.

As a safe way to manage cancer chemotherapy, a regimen registration system of chemotherapies was started in our hospital in April of 2007. Only chemotherapies registered in the regimen system can be conducted. Beginning in July of 2007, to assure safer chemotherapy, a standard clinical value of laboratory data was established as the criteria to discontinue chemotherapies. The individual laboratory data have been checked according to the discontinuance criteria by pharmacists in our hospital. With the adoption of this regimen registration system for standardized procedures of various chemotherapies, laboratory data can be checked according to the criteria, and certain chemotherapies can now be discontinued. However, in certain cases some doctors proceeded chemotherapies although pharmacists suggested that laboratory data did not meet the criteria. It is important to keep checking the registered regimen and criteria. Pharmacists have to confirm the checking system based on the patient's condition and improve the regimen system of chemotherapy more clearly together with doctors and nurses.