We evaluated the prognoses of newly diagnosed gliomas through WHO Grades II, III and IV to assess the overall tendency of treatment results for glioma in our institute. Furthermore, statistical analysis was performed to determine factors influencing the prognosis.

A total of 185 newly diagnosed glioma patients were operated on from 2000 to 2006. The primary endpoint was the overall survival from the date of surgery. The factors assessed as to whether they influenced the prognosis were the WHO grades of sex, age, location of the lesion, pre-operative Karnofsky Performance Status (KPS), extent of resection and whether or not radiation therapy was performed.

The WHO grades influenced the survival significantly (P < 0.0001). The Grades II and III showed no statistically significant difference in survival (P = 0.174), whereas Grades III and IV showed a significant difference (P < 0.0001). The factor influencing survival as well as the grades was the KPS (P < 0.0001). The comparison of survival over WHO grades in the same KPS group was performed for 2 KPS groups (KPS = 100, KPS 80–90), and these also showed significant differences (P = 0.0009 and 0.0143, respectively).

Despite the different distributions of the KPS, the Grade III glioma patients showed survival comparable to that of the Grade II. On the other hand, the Grade IV glioma patients showed significantly poorer survival compared with Grade II or III.

Genetic polymorphisms associated with breast cancer risk are likely to differ among ethnic and molecular subtypes. The ability to identify genetic polymorphisms affecting the risk of estrogen receptor (ER)-positive breast cancer may lead to the more efficient selection of candidates for chemoprevention with endocrine agents. We focused on identifying common genotypes for ER-positive breast cancer in premenopausal Japanese women.

We compared genetic polymorphisms of ER, estrogen metabolism genes (CYP17A1, CYP19A1, HSD17B1 COASY, CYP1B1 and COMT), and p53 between ER-positive and -negative female Japanese breast cancer patients, and analyzed whether these polymorphisms affected the frequency of ER-positive breast cancer.

Carriers of the G allele of ER (rs6905370) were more frequent in ER-positive breast cancer than in ER-negative breast cancer especially in those under 50-year old. Pairwise analysis showed that combinations of the ER G allele with the homozygous Trp genotype of CYP19A1 codon 39 (rs2236722), the methionine (Met) allele of COMT codon 158 (rs4680) or Pro allele of p53 codon 72 (rs1042522) were more frequent in ER-positive than ER-negative breast cancer, especially in patients less than 50-year old. The frequencies of these combinations were even higher in patients with strongly ER-positive tumors (Allred's scores of 7 or 8).

Our study demonstrated genetic polymorphisms of ER, CYP19A1, COMT and p53 genes frequently occur in ER-positive breast cancer in premenopausal Japanese women.

The overexpression of HER-2 protein has generally been considered to be consistent in primary and metastatic tumor tissues. We evaluated HER-2 protein overexpression levels in 31 autopsied cases.

Hematoxylin–eosin staining and immunohistological staining Hercep Test II^TM were performed on the primary tumors and the lung, liver, brain and bone metastatic tumors.

Nine (29%) of the 31 primary tumors were HER-2 score 3+ and HER-2 score 3+ cases were significantly more frequent in carcinomas of nuclear Grade 3 than in those of Grade 1 or 2. In these 31 patients, the HER-2 status in the primary tumors was consistent with the metastatic foci of the lung, liver, brain and bone in 96% (25 of 26), 91% (21 of 23), 100% (12 of 12) and 85% (11 of 13), respectively. With regard to the nine patients with HER-2 score 3+ primary tumors, the HER-2 status in the primary tumors was consistent with the metastatic foci of the lung, liver, brain and bone in 87% (seven of eight), 78% (seven of nine), 100% (only one) and 33% (one of three), respectively. In 11 (92%) of the 12 patients with brain metastasis, the HER-2 was not overexpressed.

Even in the far-advanced stages of autopsy, HER-2 status of the primary tumors appeared to be maintained especially in the foci of the lung, liver and brain metastases. As there was a high degree of agreement in HER-2 status between the primary tumors and the metastatic foci to the lung, liver and brain, it is considered to be reasonable to treat patients with such metastatic foci based on the HER-2 status of the primary tumors.

Since there is now growing interest in the incorporation of patient-reported outcome measures in cancer clinical trials, a patient-based questionnaire, the Patient Neurotoxicity Questionnaire (PNQ) was developed to quantify the symptoms and severity of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to evaluate the physicians’ perspectives regarding the utility and diagnostic value of PNQ.

A questionnaire was sent to 61 physicians who participated in a Phase III randomized trial of adjuvant chemotherapy in breast cancer (AC followed by taxane versus taxane alone) that used the PNQ to assess CIPN.

Forty-seven out of 61 physicians (77%) responded. The majority considered neurosensory symptoms the diagnostic hallmark for CIPN and most regarded interference with activities of daily living (ADLs) as definite justification for treatment modifications. For neurosensory disturbance, the majority of physicians indicated that Grade D severity (moderate to severe symptoms interfering with ADLs) should result in treatment postponement and Grade E severity (severe symptoms preventing most ADLs) should result in treatment discontinuation. Similarly, for neuromotor disturbance, over half of the physicians replied that Grade C (moderate symptoms not interfering with ADLs), D and E severity should result in dose reduction, treatment postponement and treatment discontinuation, respectively. Eighty-four percentage of the physicians reported that the use of the PNQ was helpful in the diagnosis and assessment of patients at risk of CIPN.

The PNQ appears to be a useful instrument for the diagnosis and grading of CIPN, as well as for clinical decision-making regarding treatment modifications secondary to CIPN.

The purpose of the retrospective analysis is to elucidate the treatment efficacy and toxicity as well as to identify prognostic factors in Japanese patients with advanced pancreatic cancer treated with gemcitabine.

Two hundred and sixty-four patients with pathologically confirmed locally advanced or metastatic pancreatic cancer, who had received gemcitabine monotherapy as first-line chemotherapy for pancreatic cancer, were analyzed. A dose of 1000 mg/m² gemcitabine was administered intravenously for 30 min on Days 1, 8 and 15 of a 28-day cycle.

One patient achieved a complete response (0.3%) and 27 patients showed a partial response (10.2%), with an overall response rate of 10.6% (95% confidence interval: 6.9–14.3%). The main grade 3/4 toxicities were neutropenia in 94 patients (35.6%) and leukocytopenia in 52 patients (19.7%). The median survival time, 1-year survival proportion and median progression-free survival time were 6.8 months, 21.6% and 3.7 months, respectively. A multivariate analysis using the Cox proportional hazards model demonstrated that a Karnofsky performance status ≥90 (P = 0.01), Stage III (P = 0.01), serum carbohydrate antigen 19-9 level <10 000 U/ml (P = 0.02), serum hemoglobin level ≥10 g/dl (P = 0.01) and serum C-reactive protein level <5.0 mg/dl (P < 0.01) were the independent favorable prognostic factors.

The treatment efficacy, toxicity and prognostic factors of single-agent gemcitabine in Japanese patients with advanced pancreatic cancer are comparable to those that have been reported in Western patients. These results may be useful as reference data in determining treatments strategies and planning for further clinical trials in Japanese patients with advanced pancreatic cancer.

Cetuximab is a chimeric IgG1 monoclonal antibody that specifically blocks the epidermal growth factor receptor. We evaluated the efficacy and safety of cetuximab in combination with irinotecan in patients with metastatic colorectal cancer (CRC) refractory to irinotecan, oxaliplatin and fluoropyrimidines.

Cetuximab was administered initially at a dose of 400 mg/m² followed by weekly infusions at 250 mg/m². Irinotecan was administered either weekly at a dose of 100 mg/m² or every 2 weeks at 150 mg/m².

Between October 2005 and February 2006, 39 consecutive patients were enrolled. The response and disease control rates (complete or partial response, or stable disease) were 30.8% (95% CI, 17.0–47.6) and 64.1% (95% CI, 47.2–78.8), respectively. With a median follow-up of 14.4 months, median time to progression was 4.1 months (95% CI, 2.7–5.1) and median survival time was 8.8 months (95% CI, 5.9–12.8). Patients (5.1%) developed Grade 3 acne-like rash.

Combination therapy of cetuximab and irinotecan is effective and well-tolerated in patients with metastatic CRC refractory to irinotecan, oxaliplatin and fluoropyrimidines.

To establish a sensitive method for the early detection of circulating tumor cells (CTCs) in peripheral blood (PB) of colorectal cancer (CRC) patients.

PB samples were collected from 156 CRC patients, 40 benign colorectal disease patients, 40 healthy individuals and 45 patients with other solid tumors. The combination of negative and positive immunomagnetic bead method was used to enrich cancer cells. Then, cytokeratin-20 (CK20), survivin and carcinoembryonic antigen (CEA) mRNA were detected by quantitative real-time reverse transcription–polymerase chain reaction (qRT–PCR). In addition, analyses were carried out for their correlation with patients’ clinicopathologic features.

The positive rates of survivin, CK20 and CEA mRNA in the PB of CRC patients were 57.7, 47.4 and 39.1%, respectively, and the sensitivity increased from 39.1% of CEA mRNA alone to 60.9% of the combined panel. The expression of the three mRNAs in CRC patients was significantly higher than that in benign control and healthy volunteers, and the expression of survivin and CK20 was not significantly higher than that of patients with other solid tumors. However, the expression of CEA mRNA was significantly higher than that of patients with other solid tumors. The expression of survivin, CK20 and CEA mRNA was significantly correlated with Dukes stages and lymph node metastasis.

The combined use of negative and positive immunomagnetic beads followed by amplification of survivin, CK20 and CEA mRNA by means of qRT–PCR is a non-invasive and sensitive assay for the detection of circulating CRC cells. The combined panel improved the sensitivity of detection in CRC patients.

This study was conducted to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in Japanese patients with Müllerian carcinoma having a therapeutic history of platinum-based chemotherapy.

Patients who were diagnosed with Müllerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of fallopian tube and peritoneal carcinoma) by histological examination and had received the initial platinum-based chemotherapy were included in the study. The study drug was administered to the patients at 50 mg/m² every 4 weeks.

Seventy-four patients were enrolled in the study. All patients had received platinum-based chemotherapy as first-line regimen and more than 90% of patients had also received taxanes. The overall response rate was 21.9% (95% confidence interval, 13.1–33.1%) and 38.4% of patients had stable disease. The median time to progression was 166 days. The major non-haematological toxicities were hand-foot syndrome (Grade 3; 16.2%) and stomatitis (Grade 3; 8.1%). Myelosuppression such as leukopenia (Grade 3; 52.7%, Grade 4; 6.8%), neutropenia (Grade 3; 31.1%, Grade 4; 36.5%) and decreased haemoglobin (Grade 3; 14.9%, Grade 4; 2.7%) were the most common haematological toxicities.

We confirmed that a 50 mg/m² every 4 weeks regimen of PLD was active in Japanese patients with Müllerian carcinoma having a therapeutic history of platinum-based chemotherapy and toxicity was manageable by dose modification of PLD or supportive care.