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Nippon rinsho. Japanese journal of clinical medicine 09/2012; 70 Suppl 7:470-4.
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Yuki Kojima, Kenji Hashimoto,
Masashi Ando,
Kan Yonemori,
Harukaze Yamamoto,
Makoto Kodaira,
Mayu Yunokawa,
Chikako Shimizu,
Kenji Tamura,
Ako Hosono,
Atsushi Makimoto,
Yasuhiro Fujiwara
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ABSTRACT: The prognosis of adult rhabdomyosarcoma (RMS) has been considered dismal. The question is raised that vincristine, d-actinomycin, and cyclophosphamide (VAC) chemotherapy may not be administered as per schedule for adult RMS; consequently, low dose intensity (DI) leads to poor prognosis. Herein, we examined whether the administration of VAC chemotherapy for adults and children with RMS is feasible with regard to the DIs of VAC.
Chart review was retrospectively performed for all identified patients. The percentage of relative DI (RDI) was calculated according to the Children's Oncology Group D9803 protocol. Further, we examined the RDI in the first 6 cycles of VAC (induction phase) and the DI after the first 6 cycles of VAC (maintenance phase).
We identified a total of 27 adults and 18 children with RMS, respectively. The mean RDIs of vincristine in total phase were significantly lower in adults than that in children (P = 0.04). In induction phase, the mean RDIs of vincristine and cyclophosphamide were similar for both groups; however, they were dropped significantly in adults during maintenance phase (P < 0.05). Mean RDIs of vincristine in elderly patients tended to become low. Low RDI was mainly attributable to hematologic toxicity, infection, and peripheral neuropathy. The prognosis of low versus high RDI was similar.
The RDIs of vincristine and cyclophosphamide in the maintenance phase were significantly lower than that in children. VAC chemotherapy for adults was not feasible; these patients require a different regimen.
Cancer Chemotherapy and Pharmacology 07/2012; 70(3):391-7. · 2.83 Impact Factor
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ABSTRACT: Information regarding hematological toxicities in breast cancer chemotherapy patients with hepatitis B (HBV) or C virus (HCV) infection is limited.
We retrospectively reviewed the presence of hepatotoxicities (i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin elevation) and hematotoxicities (i.e. leukopenia and thrombocytopenia) among breast cancer patients with HBV or HCV infection who received chemotherapy from 1999 to 2010. All of the patients included in this analysis were classified as Child-Pugh A.
Among 32 patients with HBV infection who underwent chemotherapy (total cycles, 378), 3 experienced grade 3/4 hepatotoxicities, requiring 2 treatment delays and 1 treatment revision. Further, 9 patients experienced grade 3/4 hematotoxicities; of these, 2 required treatment delays and 3 required treatment revisions. Fifty-two HCV patients underwent a total of 570 cycles of chemotherapy. Five patients experienced grade 3/4 hepatotoxicities and required treatment delays, whereas 10 patients experienced grade 3 hematotoxicities; 3 of these patients required treatment delays.
Hematotoxicities requiring chemotherapy dose or treatment revision were not highly prevalent among breast cancer chemotherapy patients with HBV or HCV infection and a normal range of liver function. Under careful monitoring, chemotherapy dosage or schedule adjustments may not be necessary in similar patients positive for HBV or HCV.
Oncology 04/2012; 82(4):228-33. · 2.27 Impact Factor
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Yuki Kojima, Kenji Hashimoto,
Masashi Ando,
Kan Yonemori,
Akihiro Hirakawa,
Makoto Kodaira,
Mayu Yunokawa,
Chikako Shimizu,
Kenji Tamura,
Noriyuki Katsumata,
Ako Hosono,
Atsushi Makimoto,
Yasuhiro Fujiwara
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ABSTRACT: Outcomes in adult patients with rhabdomyosarcoma are poor, with a 5-year survival rate of approximately 30 %. The current study aimed to compare the clinical outcomes of adult and childhood rhabdomyosarcoma patients with local and metastatic disease and to examine the impact and timing of local therapy on metastasis.
Clinicopathological features and patient outcomes were reviewed retrospectively for rhabdomyosarcoma patients receiving chemotherapy between 1981 and 2010 at our institution. Adults were defined as those aged 21 years or older.
Of the 98 patients identified, 36 were adults (median age, 29; range, 21-72) and 62 were children (median age, 11; range, 0.6-20). Median progression-free survival of localized and metastatic disease for children and adults was as follows: localized disease, 166.9 versus 22.4 months (p = 0.005), and metastatic disease, 13.3 versus 13.3 months (p = 0.949), respectively. Multivariate regression analysis revealed that older age (≥ 21 vs. <21) was a significant poor prognostic factor in localized disease. Conversely, age was not related to survival in metastatic disease. Receiving radiotherapy to the primary site was an independent factor indicating a better prognosis. An analysis of the optimal timing of local therapy was performed for 53 patients; however, its significance on survival could not be determined.
Age was a negative prognostic factor in rhabdomyosarcoma patients with localized disease, but it did not affect the survival in metastatic disease. For metastatic disease, although local therapies may be effective for survival, the timing of such therapies should be determined individually.
Journal of Cancer Research and Clinical Oncology 03/2012; 138(7):1249-57. · 2.56 Impact Factor
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ABSTRACT: Breast cancer stem cells are rich in triple negative or human epidermal growth factor receptor-2-positive breast cancers. The role of these stem cells in hormone receptor-positive breast cancers is unknown. Therefore, we launched this retrospective biomarker analysis to clarify the role of stem cells in relation with endocrine therapy in hormone receptor-positive breast cancer.
Formalin-fixed paraffin-embedded tissue samples from primary stage IV, hormone receptor-positive breast cancers prior to endocrine therapy were obtained from 4 cancer centers in Japan between 1999 and 2008. We examined the expression of ALDH1 and CD44/CD24 in breast tissue and correlated the results with response to endocrine therapy and patient prognosis.
ALDH1-positive and CD44+ CD24- cancer cells were found in 16% of 92 samples and 27% of 77 samples, respectively. Response to endocrine therapy was similar in the ALDH1-positive and ALDH1-negative tumor groups, and between CD44+ CD24- and other tumor groups. After a median follow-up period of 793 days, neither ALDH1 positivity nor CD44+ CD24- status of tumor cells was related to progression-free survival (ALDH1 positive vs. negative, 378 vs. 292 days, p = 0.53; CD44+ CD24- vs. others, 224 vs. 269 days, p = 0.52) or overall survival (ALDH1 positive vs. negative, 1,348 vs. 1,479 days, p = 0.17; CD44+ CD24- vs. others, 1,071 vs. 1,462 days, p = 0.54).
There is no correlation between biomarker expression and outcome in hormone receptor-positive breast cancer.
Oncology 03/2012; 82(3):168-74. · 2.27 Impact Factor
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ABSTRACT: Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed.
We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively. Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13. The response rate to chemotherapy was highest for the gynecological IPs. Patients with gynecological or lung cancer IPs had longer median progression-free survival than those with others: 11.2 months for gynecological IPs (p<0.001) and 6.8 months for lung IPs (p = 0.05). Lung, digestive, prostate, and gynecological profiles were associated with significantly longer median survival time than the other profiles. Multivariate analysis confirmed that the IPs were independent prognostic factors for survival.
The IPs identified in this study can be used to further stratify patient prognosis for unfavorable subsets of unknown primary adenocarcinoma.
PLoS ONE 01/2012; 7(1):e31181. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: The purpose of this work was identify potential prognostic factors for survival in patients with primary metastatic hormone receptor-positive breast cancer undergoing endocrine therapy (ET) as first-line treatment. METHODS: We investigated the clinical and pathological characteristics of 69 newly diagnosed stage IV hormone receptor-positive breast cancer patients undergoing ET between 1999 and 2009, and correlated these factors with disease progression and overall survival. RESULTS: Multivariate regression analysis revealed that progesterone receptor (PgR) positivity (hazard ratio (HR) 0.248; p = 0.001) and clinical benefits of first-line ET (HR 0.386; p = 0.008) were significant prognostic factors for survival. When first-line ET was not effective, patients for whom second-line ET was effective survived significantly longer than those for whom second-line ET was not effective (median survival time, 45.3 vs. 25.8 months; p = 0.0411). CONCLUSIONS: PgR positivity and clinical benefits of first-line ET were independent prognostic factors for patients with hormone receptor-positive stage IV breast cancer. Moreover, the benefits of second-line ET in patients with a tumor resistant to first-line ET suggests the existence of drug-specific resistance to ET.
Breast Cancer 12/2011; · 1.36 Impact Factor
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Yuko Tanabe, Kenji Hashimoto,
Chikako Shimizu,
Akihiro Hirakawa,
Kenichi Harano,
Mayu Yunokawa,
Kan Yonemori,
Noriyuki Katsumata,
Kenji Tamura,
Masashi Ando,
Takayuki Kinoshita,
Yasuhiro Fujiwara
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ABSTRACT: BACKGROUND: The long-term outcomes and risk factors of paclitaxel-induced peripheral neuropathy (PIPN) have not yet been fully elucidated. METHODS: We identified 219 breast cancer patients who received paclitaxel as adjuvant chemotherapy between 2002 and 2009. We retrospectively analyzed the incidence, time to onset, duration, and risk factors for PIPN by chart review. RESULTS: Of the 219 patients, 212 developed PIPN (97%) during a median follow-up time of 57 months (range 5.3-95.5). Median time to PIPN onset was 21 days (range 11-101) for the entire patient population: 35 days (range 14-77) for weekly administration and 21 days (range 11-101) for tri-weekly administration. PIPN caused termination of paclitaxel treatment in 7 patients (4%). Median duration of PIPN was 727 days (range 14-2621 days). PIPN persisted in 64 and 41% of patients at 1 and 3 years after initiating paclitaxel, respectively. Age ≥60 years and severity of PIPN were significantly associated with PIPN duration. CONCLUSIONS: PIPN persists longer in older patients and in those who experience severe neuropathy. Further studies to identify the risk factors for PIPN are warranted.
International Journal of Clinical Oncology 11/2011; · 1.41 Impact Factor
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ABSTRACT: We conducted phase I and tolerability studies to determine the maximum tolerated dose (MTD) and recommended dose of nab-paclitaxel when administered weekly with solid tumors and to evaluate the tolerability of weekly administration at a dose of 150 mg/m(2) with metastatic breast cancer (MBC) as a first-line therapy in Japanese patients.
In this phase I study, patients with advanced solid tumors received nab-paclitaxel at dose levels of 80-125 mg/m(2) as 30-min infusions once a week for three weekly doses repeated every 4 weeks. In the tolerability study, patients received 150 mg/m(2) nab-paclitaxel. Blood samples at the first dose of nab-paclitaxel were collected for pharmacokinetic analysis.
Fifteen patients were treated for a median of five cycles in the phase I study. The MTD was 125 mg/m(2); the dose-limiting toxicity was neutropenia requiring skipping of the second or third weekly administration in the first cycle. In the tolerability study, six patients were treated for a median of six cycles; no intolerable toxicities were observed in the first cycle. Grade 3 sensory and motor neuropathy was observed in four and one patients, respectively. Ocular toxicities were observed in two patients (keratopathy and macular hole). Maximum paclitaxel concentration and area under the curve increased linearly with the dose.
Weekly administration of nab-paclitaxel was well tolerated up to 100 mg/m(2) by heavily pretreated patients. For MBC patients, 150 mg/m(2) nab-paclitaxel as a first-line therapy was well tolerated. Dose reduction due to neuropathy allows multiple cycles of treatment.
Cancer Chemotherapy and Pharmacology 08/2011; 69(2):457-65. · 2.83 Impact Factor
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ABSTRACT: To examine the use of squamous cell carcinoma antigen (SCCA) as a biomarker of chemotherapy response in patients who underwent chemotherapy for metastatic cervical carcinoma.
The study population consisted of patients who underwent first-line chemotherapy for metastatic cervical carcinoma between 1999 and 2009. SCCA levels were serially measured before, during and after chemotherapy. Radiographic responses were evaluated according to the criteria of the World Health Organization. A logistic model was used to determine the best prediction model, and internal and external validation of the prediction model were performed to compare the areas under the receiver operating characteristic curves (AUCs).
In total, 55 patients were included in the analysis. Data for 32 patients enrolled in various clinical trials were used to develop the prediction model. Patients who achieved a radiographic response showed a significant decline in SCCA levels between the second and third cycles of chemotherapy, whereas patients who did not achieve a radiographic response showed constant SCCA levels over the same period. The prediction model was developed on the basis of changes in the SCCA level between the second and third cycles of chemotherapy (AUC=0.832) and the baseline SCCA level. The AUC after external validation, calculated using the data of the clinical practice population (n=22), was 0.871.
A response to chemotherapy was possible for patients in whom SCCA levels declined between the second and third cycles of chemotherapy.
European journal of obstetrics, gynecology, and reproductive biology 08/2011; 159(2):394-8. · 1.97 Impact Factor
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ABSTRACT: PARP and BRCA are both known as DNA repair enzymes. Functional loss of BRCA cell with PARP inhibition indicates apoptosis. Triple negative breast(TNB)cancer(estrogen receptor-negative, progesterone receptor-negative, HER-2 expression negative)are well associated with basal-type breast cancer. Basal-type breast cancer often has loss of BRCA and showed poor clinical outcomes. Considering the similar molecular profiles of Basal-type breast cancer and TNB cancer, clinical trials using PARP inhibitor for patients with TNB cancer has been warranted. A randomized phase II trial comparing gemcitabine and carboplatin(GC)to GC plus BSI-201(PARP inhibitor)in patients with metastatic TNB cancer showed significantly longer progression-free survival and overall survival. We herein summarized up-to-date knowledge of PARP inhibitor in association with TNB and BRCA.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2010; 37(7):1187-91.
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Kenji Hashimoto,
Hiroyuki Fujimoto,
Tsutomu Kouno,
Masahiro Koseki,
Kan Yonemori,
Taizo Hirata,
Mayu Yunokawa,
Chikako Shimizu,
Noriyuki Katsumata,
Kenji Tamura,
Masashi Ando,
Masahiro Takeuchi,
Hiroyuki Nakanishi,
Motokiyo Komiyama,
Tohru Nakagawa,
Yasuhiro Fujiwara
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ABSTRACT: The optimal management of extragonadal germ cell tumor (EGGCT) and metachronous testicular germ cell tumor (MTGCT) has not been determined.
Fifty-one consecutive patients with EGGCT were identified. Testicular palpation or ultrasonography to rule out a primary testicular tumor was performed. Pretreatment testicular biopsies were not performed. The incidence and outcome of MTGCT, and the prognosis of EGGCT were evaluated.
Twenty-five and 26 patients, respectively, had mediastinal and retroperitoneal EGGCT. Fourteen and 37 patients, respectively, had seminoma and nonseminoma. Five patients developed MTGCT in patients with retroperitoneal EGGCT. The median interval from the primary treatment for EGGCT to MTGCT diagnosis was 64 months (range 15-120). The cumulative risk of developing MTGCT was 8.3% at 6 y. Five patients underwent an orchiectomy and have survived in the 16-months median follow-up period (range 4-30). Among the patients with seminomatous and nonseminomatous EGGCT, the 5-year survival rate was 84.6% and 78.3%, respectively. Among the patients with retroperitoneal and mediastinal nonseminomatous EGGCT, the 5-year survival rate was 94.7% and 58.8%, respectively.
The prognosis of EGGCT without testicular biopsies was sufficient. EGGCT patients, especially retroperitoneal EGGCT, need long-term follow-up for MTGCT.
Urologic Oncology 05/2010; 30(3):319-24. · 3.22 Impact Factor
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Kenji Hashimoto,
Kan Yonemori,
Chikako Shimizu,
Akihiro Hirakawa,
Harukaze Yamamoto,
Makiko Ono,
Taizo Hirata,
Tsutomu Kouno,
Kenji Tamura,
Noriyuki Katsumata,
Masashi Ando,
Yasuhiro Fujiwara
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ABSTRACT: This study aims at evaluating the impact of age on patterns of care in elderly patients with metastatic breast cancer (MBC) and their outcome. We identified 177 patients aged ≥ 65 treated for MBC at the National Cancer Center Hospital in Japan from 1999 to 2007. We evaluated the impact of age on the selection of best supportive care (BSC) only, chemotherapy as first-line treatment, and chemotherapy after first-line endocrine therapy. Fisher's exact test and a multivariate logistic regression analysis with variables of age, performance status (PS), hormone receptor (HR) status, human epidermal growth factor-2 (HER2), and life-threatening disease (LTD) were used. The median age of patients was 72, and 60 patients (33.9%) were aged ≥ 75. HR-negative patients and those whose PS was ≥ 2, regardless of age, were more likely to choose BSC without chemotherapy. Multivariate analysis revealed age ≥ 75 (P = 0.018), positive-HR status (P < 0.001), and absence of LTD (P < 0.001) were significantly correlated to choose endocrine therapy rather than chemotherapy. In patients who had previous endocrine therapy, age (P = 0.008) and absence of HER2 (P = 0.018) were related not to choose chemotherapy. Not age but HR-negative status or PS ≥ 2 were related to the selection of BSC. In selecting endocrine therapy rather than chemotherapy, age (≥ 75), HR-positive, and absence of LTD were significant factors. In patients failed to endocrine therapy, age and HER2 status were correlated to decision-making to choose chemotherapy.
Medical Oncology 03/2010; 28(2):434-40. · 2.14 Impact Factor
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ABSTRACT: The purpose of this study was to identify factors that affect the duration of the interval between the completion of palliative chemotherapy and death.
We retrospectively analyzed 255 cases in which patients had received palliative chemotherapy in the medical oncology division and died during the period 2002-2006. Univariate and multivariate analyses were performed to identify factors that affected the duration of the interval between the completion of chemotherapy and death.
There were 133 cases of breast cancer, 77 cases of gynecological cancer, 24 cases of primary unknown cancer, and 21 cases of other cancers. The median interval between the completion of chemotherapy and death was 100 days (range, 5-1,206 days). Thirty-two patients (12.6%) died within 30 days, and 82 patients (32.3%) died within 60 days. Fifty-eight (22.7%) patients were symptomatic when chemotherapy was started, and 205 patients (80.4%) were provided information about palliative care units at the start of chemotherapy. The factors associated with a short interval between the completion of chemotherapy and death (< or = 90 days) according to the univariate analysis were male sex, young age (< or = 45 years), attending physician, poor Eastern Cooperative Oncology Group performance status score (3 or 4), obvious symptoms, and not having been given information about palliative care units. The results of the multivariate analysis indicated that young patients (< or = 45 years) who had not been referred to a palliative care unit and who had symptoms survived for a significantly shorter time interval.
Young patients who were symptomatic tended to choose chemotherapy instead of entering a palliative care unit until the very near-the-end-of-life stage.
The Oncologist 07/2009; 14(7):752-9. · 3.91 Impact Factor
