Hiroshi Tsubamoto

Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

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Publications (34)59.71 Total impact

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    ABSTRACT: Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.
    Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 07/2014;
  • Hiroshi Tsubamoto, Takashi Sonoda, Kayo Inoue
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    ABSTRACT: Background/Aim: Recurrent triple-negative breast cancer (TNBC) patients have poor prognoses and limited treatment options, especially after progression during prior chemotherapy. The present study aimed to determine the impact of itraconazole with chemotherapy in these patients. Patients and Methods: Medical records of recurrent TNBC patients receiving itraconazole with chemotherapy between 2008 and 2012 were retrospectively reviewed. Results: Thirteen patients who progressed during prior chemotherapy (12 with visceral organ metastases) were enrolled. All patients had received docetaxel, carboplatin, and gemcitabine with itraconazole. Additionally, 3 patients with pleural effusion and 2 with inflammatory breast cancer received bevacizumab. No febrile neutropenia, platelet transfusion, or chemotherapy-related death was observed during treatment with itraconazole. The response rate, median progression-free survival, and median overall survival were 62% (95% confidence interval (CI): 35-88%), 10.8 months (95%CI: 7.6-15.3 months), and 20.4 months (95%CI: 13.1-41.4 months), respectively. Conclusion: Chemotherapy with itraconazole is promising for heavily pre-treated TNBC patients.
    Anticancer research 07/2014; 34(7):3839-44. · 1.71 Impact Factor
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    ABSTRACT: Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥50 mg/m(2)). Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy). Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each). Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.
    Supportive Care in Cancer 05/2014; · 2.09 Impact Factor
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    ABSTRACT: After progression during chemotherapy, persistent ovarian cancer rarely responds to cytotoxic agents. We evaluated the use of adjunctive itraconazole for treating refractory ovarian cancer. Medical records of patients with ovarian cancer were retrospectively reviewed to select those with a history of platinum and taxane administration, clinical progression within six months of the last platinum administration, continuation of chemotherapy after the first progression during chemotherapy. Among 55 patients, itraconazole in combination with chemotherapy was administered to 19 patients. The median progression-free survival (PFS) was 103 days and 53 days for chemotherapy with and without itraconazole, respectively (p=0.014). The corresponding median overall survival was 642 days and 139 days, respectively (p=0.006). The hazard ratio for PFS was 0.24 (p=0.002) and for overall survival was 0.27 (p=0.006) for therapy with itraconazole. Adjunctive itraconazole is promising for patients with refractory ovarian cancer.
    Anticancer research 05/2014; 34(5):2481-7. · 1.71 Impact Factor
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    ABSTRACT: Recurrent ovarian clear cell carcinoma (CCC) rarely responds to cytotoxic agents. Itraconazole is a potent inhibitor of the P-glycoprotein efflux pump, angiogenesis, and the Hedgehog pathway. We evaluated the efficacy of chemotherapy with itraconazole for CCC. Medical charts of patients with CCC who had received chemotherapy with itraconazole were retrospectively reviewed. Among nine patients with CCC, five had a history of progression with paclitaxel and carboplatin, and none had received prior treatment with bevacizumab or other targeted therapy. Eight patients received docetaxel (35 mg/m(2), day 1) and carboplatin-based (area under the curve, 4 mg·min(-1)·mL(-1); day 1) chemotherapy with an oral itraconazole solution (400 mg, days -2 to 2), repeated every two weeks. The response rate, median progression-free survival and overall survival were 44% (95% confidence interval [(CI)=12-77%], 544 days (95% CI=82-544 days) and 1,047 days (95% CI=462-1332 days), respectively. Chemotherapy with itraconazole is promising for patients with CCC.
    Anticancer research 04/2014; 34(4):2007-14. · 1.71 Impact Factor
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    ABSTRACT: •Endometrioid adenocarcinoma may develop during the long-term follow-up of APA.•Atypical polypoid adenomyoma is a precursor of endometrioid adenocarcinoma.•Careful follow-up is needed for the conservative management of APA.
    Gynecologic oncology case reports. 04/2014; 8:21-3.
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    ABSTRACT: The ideal timing for transition to best supportive care (BSC) for ovarian cancer patients is not clear. We retrospectively assessed the survival benefit of continuing chemotherapy and hospice enrollment in late-stage ovarian cancer patients. Eligibility criteria included platinum and taxane treatment, clinical progression within 6 months of the last platinum dose, and progression during chemotherapy. Of the 55 eligible patients (median overall survival after first becoming refractory [1st Ref], 96 days), 22 received chemotherapy (Chemo group), two received radiation therapy, and 13 had medical contraindications for subsequent chemotherapy. The remaining 18 patients (BSC group) were compared with the Chemo group. The Chemo and BSC groups had similar background characteristics, except for the rate of consultation with a regional palliative care physician before or within 1 week of 1st Ref (9% vs 50%, respectively). In multivariate analysis, chemotherapy (hazard ratio 0.251, P = 0.005) and hospice enrollment (hazard ratio, 0.274, P = 0.023) were predictive factors of survival after 1st Ref. Chemotherapy after 1st Ref can be offered and hospice enrollment during the terminal stages is encouraged for recurrent ovarian cancer patients.
    Journal of Obstetrics and Gynaecology Research 03/2014; · 0.84 Impact Factor
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    ABSTRACT: Patients with hereditary cancer need an integrated support system. A recently launched project was evaluated in terms of its efficacy in screening patients with hereditary cancer at the gynecologic service. The project team comprised gynecologists, surgeons, medical geneticists, and certified genetic counselors (CGCs) in our hospital. At the gynecologic service, a newly developed self-administered family history questionnaire (SAFHQ) was given to patients with ovarian, endometrial, or breast cancer as well as a history of multiple cancers. After an interview, a CGC constructed a pedigree and evaluated the risk for hereditary cancer. Patients at risk were recommended by a gynecologist to receive further genetic counseling at the Department of Genetics according to the modified Bethesda criteria, Amsterdam II criteria, and National Comprehensive Cancer Network (NCCN) guidelines 2012 for breast-ovarian cancer syndrome (HBOC). The numbers of newly screened patients were compared before and after the project launch. The SAFHQ was administered to 131 patients and 106 (81 %) pedigrees were constructed between August 2012 and July 2013. The number of newly screened patients according to the Bethesda criteria was 4 and 8 at 10 years before and 1 year after the project launch, respectively. Two and 31 patients met the NCCN criteria for HBOC excluding ovarian cancer alone, respectively, at these 2 time points. Of 54 patients who were recommended to undergo further counseling, 10 (19 %) visited the Department of Genetics. After the launch of an integrated support system, the number of patients with hereditary cancers who were screened increased. The gynecologic service played a pivotal role in patient and family care.
    International Journal of Clinical Oncology 12/2013; · 1.41 Impact Factor
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    ABSTRACT: Maximum standardized uptake value on (18) F-fluorodeoxyglucose positron emission tomography was evaluated as a predictive surrogate marker in developing treatment strategies for recurrent or metastatic endometrial stromal sarcoma. Clinical information was obtained from records of patients with recurrent or metastatic endometrial stromal sarcoma who underwent surgery or biopsy following (18) F-fluorodeoxyglucose positron emission tomography. Pathological features - including estrogen receptor, progesterone receptor and Ki-67 expression - were immunohistochemically evaluated. We classified lesions as 'positron emission tomography positive' if the maximum standardized uptake value was 3.0 or higher. Clinicopathological features were compared between patients with positive and negative positron emission tomography findings by using the χ(2) -test. Among eight recurrent and one metastatic endometrial stromal sarcoma patients, four (44%) had positron emission tomography-positive findings. Two positron emission tomography-positive patients were estrogen receptor negative and the five positron emission tomography-negative patients were estrogen receptor positive (P = 0.073). The Ki-67 index was 10% or higher in the four positron emission tomography-positive patients, but less than 5% in the five positron emission tomography-negative patients (P = 0.003). Three patients with positron emission tomography-positive tumors received more aggressive treatment (e.g. cytotoxic chemotherapy and additional surgery) than did those with positron emission tomography-negative tumors. One patient who died of disease had positron emission tomography-positive tumors, was negative for estrogen and progesterone receptors, and had a 20% Ki-67 index. (18) F-Fluorodeoxyglucose uptake was associated with tumor biology of recurrent or metastatic endometrial stromal sarcoma. (18) F-fluorodeoxyglucose-positron emission tomography was useful for developing treatment strategies for recurrent or metastatic endometrial stromal sarcoma.
    Journal of Obstetrics and Gynaecology Research 10/2013; · 0.84 Impact Factor
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    ABSTRACT: The aim of this study was to identify prognostic factors associated with neoadjuvant transuterine arterial chemotherapy (TUAC) followed by type III radical hysterectomy. The medical histories of patients with stage IB2 to IIB cervical cancer who received neoadjuvant TUAC between 1996 and 2009 at our institution were retrospectively reviewed. Seventy-three patients received TUAC using cisplatin combined with intravenous nedaplatin, irinotecan, paclitaxel, or etoposide administration. Forty-seven patients (64%) had squamous cell carcinoma. The radiological response rate was 96% (95% confidence interval, 91%-100%). Radical hysterectomy was completed for 95% of enrolled patients. Examination of the resected cervical specimens showed that tumor cells were absent in 19 cases and stromal invasion was less than 3 mm in 7 cases. Among these 26 patients, 23 (32%) had pathologically negative pelvic lymph nodes and no recurrence during the follow-up period. The 5-year relapse-free survival and overall survival rates were 69% and 74%, respectively. Among 23 patients with recurrence or progressive disease, the median survival time after recurrence or progression was 12 months. In multivariate analysis, a tumor size of more than 60 mm and pathological positive lymph nodes were negative prognostic factors for overall survival. Tumor size, pathological response, and lymph node metastases were prognostic factors for cervical cancer. The high pathological response rate associated with TUAC makes it a promising treatment for bulky cervical cancer.
    International Journal of Gynecological Cancer 10/2013; 23(8):1470-1475. · 1.94 Impact Factor
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    ABSTRACT: BACKGROUND: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of irinotecan plus carboplatin chemotherapy in patients with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Patients with either radiologically- or serologically-recurrent EOC were administered intravenous irinotecan (60 mg/m2; days 1 and 8) and carboplatin area under the curve of 5 mg/ml/min (day 1), repeated every 21 days. The primary end-point was response rate (RR), while the secondary end-points were adverse events and progression-free survival (PFS). RESULTS: Between 2005 and 2009, 40 patients (median age=59 years) with EOC were enrolled. Intention-to-treat analysis showed an RR of 43% [95% confidence interval (CI)=27-58%]. For patients with a platinum-free interval (PFI) of <6 months, overall RR based on RECIST was 21% (95% CI=0-43%) and median PFS was 3.7 months (95% CI=2.5-7.7 months), while those in patients with PFI ≥6 months were 52% (95% CI=31-74%) and 9.1 months (95% CI=7.9-11.2 months), respectively. Grade 3/4 toxicity encountered during the first cycle included G3/G4 neutropenia in 65% of patients (12/14), G3/G4 thrombocytopenia in 48% (18/1), G3 febrile neutropenia in 5% (2), G3 nausea in 5% (2), G3 diarrhea in 5% (2), and G3 fatigue in 5% of patients (2). CONCLUSION: This carboplatin plus irinotecan combination demonstrated a modest activity in recurrent EOC. However, considering its hematological toxicities, the regimen should be further investigated to establish the feasibility of the modified dose for platinum-sensitive disease.
    Anticancer research 03/2013; 33(3):1073-1079. · 1.71 Impact Factor
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    ABSTRACT: OBJECTIVE: A phase II trial on neoadjuvant trans-uterine arterial chemotherapy (TUAC) followed by type III radical hysterectomy (RH) was conducted for patients with bulky cervical adenocarcinoma (AC). METHODS: Tumors of >4cm were eligible. The neoadjuvant regimen comprised paclitaxel (60mg/m(2) intravenously on days 1, 8, and 15) and cisplatin (70mg/m(2) TUAC followed by transcatheter embolization with gelatin sponge particles on day 2) repeated every 3weeks for 3cycles. The primary endpoints were clinical and pathological responses. RESULTS: Twenty-two patients (median age, 51years; range, 33-75years) were enrolled. The International Federation of Gynecology and Obstetrics stages were IB2 (9 patients), IIA-IIB (8), IIIB (3), and IVA (2). The adeno/adenosquamous ratio was 16/6. The overall clinical response rate was 95.4% (95% confidence interval [CI], 86.7-100%). RH was completed in 19 patients (86%), including 2 stage IVA patients who underwent anterior or posterior pelvic exenteration. Of the 19 patients, no residual malignant cells were found pathologically in 4; thus, the pathological complete response rate was 18% (4/22). No patients experienced grade 4 thrombocytopenia or febrile neutropenia or required platelet transfusions. The 5-year progression-free survival and overall survival rates in stages IB2-IIB were 70.0% (95%CI, 48.1-92.1%) and 69.5% (95%CI, 47.0-92.0%), respectively. The 2 patients with stage IVA tumors were alive without recurrence for 72 and 84months after enrollment. CONCLUSIONS: TUAC showed high clinical and pathological response rates. TUAC is promising for stage IB2-IIB and IVA bulky AC.
    Gynecologic Oncology 01/2013; · 3.93 Impact Factor
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    ABSTRACT: •Occult ovarian carcinoma of presumable fallopian tube origin in Lynch syndrome•Atypical endometrial hyperplasia during a 10-year follow-up period after colon cancer•Synchronous ovarian serous carcinoma in situ and borderline tumor in Lynch syndrome.
    Gynecologic oncology case reports. 01/2013; 5:61-3.
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    ABSTRACT: •A second case of low-grade myofibroblastic sarcoma of the vulva.•Six-year follow-up with no evidence of disease after radical local excision.•Adequate margin resection is important.
    Gynecologic Oncology Case Reports. 01/2013; 5:34–36.
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    ABSTRACT: •Multiple bone metastases following cervical cancer was completed resolved.•Metastatic lesions were present within a previously irradiated zone of primary external radiation.•Concurrent chemotherapy and bisphosphonate administration is promising.
    Gynecologic oncology case reports. 01/2013; 5:22-4.
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    ABSTRACT: Early detection of ovarian pregnancy (OP) is essential for successful laparoscopic conservative surgery. However, early preoperative ultrasonography-based diagnosis is often difficult when fetal cardiac activity or the yolk sac is absent. The authors report a case of OP diagnosed at eight weeks gestational age in a natural pregnancy. The patient presented with amenorrhea and transient vaginal bleeding, and slight tenderness in the right ovary was noted during vaginal ultrasonography. Furthermore, ultrasonography showed a gestational sac (GS) without fetal cardiac activity or yolk sac, consistent with OP, and an adjacent compressible lutein cyst. The uterus, fallopian tubes, and left ovary were normal, and no cul-de-sac blood or ascites were found. Laparoscopy showed a two-cm mass partially covering the right ovary, which contained an unruptured GS. Subsequently, the mass was removed, and OP was histologically confirmed.
    Clinical and experimental obstetrics & gynecology 01/2013; 40(4):604-6. · 0.38 Impact Factor
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    ABSTRACT: Glassy cell carcinoma (GCC) of the cervix is rare and aggressive.A few case reports have described a response to intravenous chemotherapy for this malignancy.This is the first report of a GCC case that responded to a combination of docetaxel and carboplatin.
    Gynecologic Oncology Case Reports. 01/2013; 6:19–21.
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    ABSTRACT: •A seminoma developed in a patient with androgen insensitivity syndrome.•The patient had a de novo androgen receptor mutation.•Proper management of AIS, including appropriate genetic counseling, is necessary.
    Gynecologic oncology case reports. 01/2013; 5:16-8.
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    ABSTRACT: OBJECTIVE: Intraperitoneal chemotherapy (IP) is known to be effective after optimal primary debulking surgery (PDS) for ovarian cancer (OC). Here, we conducted a phase II study to investigate its effectiveness after interval debulking surgery (IDS). METHODS: Thirty-seven patients with FIGO stage IIIB-IV and suboptimal (≥1cm diameter) residual disease after PDS were enrolled. Carboplatin (AUC 4 IV, Day 1) and cisplatin (50mg/m(2) IV, Day 3) were given q21d for 3cycles. After IDS, paclitaxel (175mg/m(2) IV Day 1 or 60mg/m(2) IV Days 1, 8, and 15, since 2000) and cisplatin (75mg/m(2) IP Day 2) were given q21d for 4cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and adverse events (CTCAE ver. 2.0). Clinical manifestations at first recurrence and subsequent treatment were also surveyed. RESULTS: Of the 37 patients, high-grade, serous adenocarcinoma was found in 33. Stages IIIB, IIIC, and IV were found in 2, 24, and 11 patients, respectively. After IDS, 23 patients had no macroscopic residual tumor. No patients had permanent enterostomy, febrile neutropenia, or platelet transfusion. The treatment protocol was completed in 22 patients, and discontinued in 5 due to IP catheter-related complications. Median PFS and OS were 22 and 57months, respectively. Among the 28 patients with recurrence, 10 had no intraperitoneal disease at first recurrence. Among the 8 patients who underwent surgical cytoreduction, 6 had no residual tumor, while 2 had a <1-cm-diameter residual tumor. CONCLUSION: IP after IDS for patients with initially suboptimally debulked OC was effective.
    Gynecologic Oncology 10/2012; · 3.93 Impact Factor
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    ABSTRACT: Fertility-sparing management for bulky cervical cancer remains under investigation. We investigated the safety of neoadjuvant transuterine arterial chemotherapy (TUAC) followed by a simple vaginal trachelectomy for patients with tumors larger than 3 cm in diameter who desired uterine preservation. First, to assess the safety and efficacy of TUAC, survival and pathological complete response data from 39 patients with a diagnosis of stage IB2 to stage IIB cervical cancer who participated in 2 consecutive trials during 1997-2006 were analyzed. The neoadjuvant chemotherapy regimens were a combination of TUAC using cisplatin with intravenous nedaplatin or irinotecan. Second, to assess the safety of fertility-sparing management with TUAC, medical records of patients matching the following criteria were reviewed during the same period: (1) International Federation of Gynecology and Obstetrics stages IB1 to IIA; (2) maximum diameter of tumor, 3 cm or more; (3) squamous cell carcinoma; (4) no radiological findings of lymph node metastasis; and (5) patient's strong desire for preservation of the uterus and to undergo TUAC. The overall 5-year survival rate of the 39 enrolled patients was 81.0% (95% confidence interval, 64.8%-93.7%). No malignant cells were found in pathologically examined surgical specimens from 14 patients (35.9%), all of whom were alive without recurrence for more than 7 years after treatment. Based on medical records, 7 patients were eligible according to the fertility-sparing criteria, 1 patient with International Federation of Gynecology and Obstetrics stage IB1 cancer, 5 patients with stage IB2, and 1 patient with stage IIA. One patient with stage IB1 cancer and 2 patients with stage IB2 cancer underwent simple vaginal trachelectomy, resection of paracervical tissues, and abdominal lymphadenectomy. Their disease-free intervals were 86, 120, and 65 months, respectively. All 3 patients had regular menses after surgery but no pregnancies, for personal reasons unrelated to fertility. Powerful neoadjuvant chemotherapy regimens resulted in a pathological complete response. Long-term disease-free interval was achieved after fertility-sparing management for bulky cervical cancer in 3 cases.
    International Journal of Gynecological Cancer 06/2012; 22(6):1057-62. · 1.94 Impact Factor