Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study.

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis.

Monitoring the impact of a national HPV vaccination program in Japan (MINT Study): rationale, design and methods.

We have developed a collaborative hospital-based approach to monitoring the impact of a human papillomavirus vaccine on cervical cancer, its precursor lesions and human papillomavirus type-specific prevalence in Japan. The monitoring will be conducted for a total period of 21 years on women aged <40 who are newly diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia or adenocarcinoma in situ at 21 participating institutes. Women are monitored to determine their vaccine history and will be human papillomavirus-genotyped each year.

Efficacy of quadrivalent human papillomavirus (types 6, 11, 16 and 18) vaccine (GARDASIL) in Japanese women aged 18-26 years.

A randomized double-blind placebo-controlled phase II trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types most frequently associated with cervical cancer (types 16/18) and genital warts (types 6/11) in Japanese women aged 18-26 years. Participants were randomly assigned to either quadrivalent HPV (types 6/11/16/18) L1 virus-like particle vaccine (GARDASIL) (n = 509) or placebo (n = 512). Participants underwent regular gynecological examinations, cervicovaginal sampling for HPV DNA, testing for serum neutralizing antibodies to HPV and Papanicolau testing.

Docetaxel/irinotecan combination chemotherapy in platinum/taxane-refractory and -resistant ovarian cancer: JGOG/WJGOG Intergroup Study.

Background: The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment.

Patients And Methods: Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m(2) (day 1) and irinotecan 60 mg/m(2) (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease.

A phase II clinical trial of topotecan in Japanese patients with relapsed ovarian carcinoma.

Objective: This Phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of topotecan in Japanese patients with relapsed ovarian carcinoma.

Methods: Patients with relapsed ovarian carcinoma after having received one regimen containing platinum-based chemotherapy were eligible for this study. Topotecan was administered at 1.

Randomized phase II trial of paclitaxel plus carboplatin therapy versus irinotecan plus cisplatin therapy as first-line chemotherapy for clear cell adenocarcinoma of the ovary: a JGOG study.

Introduction: Paclitaxel plus carboplatin (TC) is generally considered to be the "gold standard" regimen for treatment of epithelial ovarian carcinomas. Little data are available, however, on the use of this regimen in patients with clear cell adenocarcinoma of the ovary (CCC). Combination chemotherapy with irinotecan hydrochloride plus cisplatin has been reported to be effective for primary and recurrent or resistant CCC.

Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial.

Background: Paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced ovarian carcinoma. Attempts to improve patient survival by including other drugs have yielded disappointing results. We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer.

Favourable prognosis with modified dosing of docetaxel and cisplatin in Japanese patients with ovarian cancer.

Background: The long-term efficacy and safety of docetaxel/cisplatin as first-line chemotherapy in Japanese patients was evaluated in order to find an optional regimen for ovarian cancer.

Patients And Methods: Women with surgically resected stage Ic-IV epithelial ovarian cancer were treated with docetaxel 70 mg/m2 and cisplatin 60 mg/m2 every 4 weeks.

Results: Ninety women were enrolled of whom 89 (median age, 54 years) received a median of 6 cycles (range 1 to 9).

Phase II clinical trial of pegylated liposomal doxorubicin (JNS002) in Japanese patients with mullerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of fallopian tube, peritoneal carcinoma) having a therapeutic history of platinum-based chemotherapy: a Phase II Study of the Japanese Gynecologic Oncology Group.

Objective: 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.

Methods: 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/m(2) every 4 weeks.

Randomized phase II study of immunomodulator Z-100 in patients with stage IIIB cervical cancer with radiation therapy.

Objective: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy.

Methods: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period.

Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.

Background: To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer.

Methods: Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy.

[A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer].

Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m2 as Level 1 or at 90 mg/m2 as Level 2 was administered on Days 1 and 29 of treatment.

Phase II trial of 3-h infusion of paclitaxel in patients with adenocarcinoma of endometrium: Japanese Multicenter Study Group.

Objective: We assessed the antineoplastic effect and adverse reactions of paclitaxel monotherapy with paclitaxel 210 mg/m(2) given every 3 weeks by 3-h infusion on patients with endometrial cancer given as a 3-h infusion.

Methods: This study was a multi-center, open-label phase II clinical trial of paclitaxel 210 mg/m(2) given every 3 weeks by 3-h infusion. Patients with advanced or recurrent endometrial cancer were enrolled.

Association of PTEN mutation with HPV-negative adenocarcinoma of the uterine cervix.

Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections.

Platelet-derived endothelial cell growth factor predicts of progression and recurrence in primary epithelial ovarian cancer.

We investigated the clinical significance of platelet-derived endothelial cell growth factor (PD-ECGF) as measured by enzyme-linked immunosorbent assay in primary epithelial ovarian cancers (EOC), finding amounts to be significantly greater in cancers than in normal ovarian tissue (p<0.01). PD-ECGF was significantly more abundant in stages III and IV than in lower stages (p<0.

Japanese ovarian trials: focus on irinotecan.

Irinotecan (CPT-11, Camptosar) has achieved a response rate of 23.6% in recurrent ovarian cancer. Irinotecan/cisplatin combination chemotherapy has shown a response rate of 33% in platinum-resistant ovarian cancer, and 76% when used as the initial regimen for ovarian cancer.

Antitumor activity of new combination chemotherapy with irinotecan hydrochloride and nedaplatin against human cervical cancer cell lines.

Antitumor activity of combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin was compared to that with CPT-11 and cisplatin. In vitro cytotoxicity of SN-38 (an active metabolite of CPT-11) in combination with nedaplatin or cisplatin was evaluated using three human cervical cancer cell lines (ME-180, CaSki and SiHa). IC50 values of nedaplatin against these three human cervical cancer cell lines were about 2-fold as high as those of cisplatin, indicating somewhat weak cytotoxic effects of nedaplatin.

The effect of granisetron on in vitro metabolism of paclitaxel and docetaxel.

Purpose: Paclitaxel and docetaxel are effective anticancer agents; however, these agents can be associated with the debilitating side effects of nausea and vomiting, thereby necessitatingthe administration of concomitant antiemetic agents. This increases the potential fordrug-drug interactionsthrough inhibition or induction of the cytochrome P450 (CYP) enzymes. The 5-HT3-receptor antagonists are currently regarded as the antiemetic 'gold standard' and this study was undertaken to investigate the effects of granisetron on the metabolism of paclitaxel and docetaxel in human liver microsomal preparations in vitro.

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report.

Background: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC.

Clinical usefulness of macrophage colony-stimulating factor for ovarian cancers: Long-term prognosis after five years.

We performed a randomized double blind study between 1992 and 1995 in which 214 patients with FIGO stage I to III ovarian cancers received administration of 10(6) units (low dose group) or 8x10(6) units (high dose group) of macrophage colony-stimulating factor (M-CSF) after cyclophosphamide/adriamycin/cisplatin (CAP) therapy. The period required to finish a set of intensive chemotherapy, which was the primary endpoint, was significantly shortened (p=0.0004), and the incidence of febrile neutropenia significantly decreased (p=0.

Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer.

Objective: To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer.

Methods: Twenty-six patients with previously untreated advanced epithelial ovarian cancer were enrolled in this study. CPT-11 60 mg/m(2) was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m(2) on day 1.

Phase I studies of nogitecan hydrochloride for Japanese.

Background: SmithKline Beecham synthesized camptothecin analogs and identified nogitecan hydrochloride (topotecan) with a broad spectrum of antitumor activity and less toxicity than camptothecin. Because preclinical and overseas clinical data indicated the antitumor effect of nogitecan hydrochloride with a 5-day repeat-dose schedule, we carried out phase I studies in Japan to determine the maximum tolerated dose (MTD), pharmacokinetics, and antitumor effect of nogitecan hydrochloride.

Methods: Phase I studies of nogitecan hydrochloride given by single and 5-day repeat dosing were carried out in patients with various solid tumors at 15 medical institutions in Japan.