[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to investigate the correlation of pretreatment and posttreatment measurements as the mean apparent diffusion coefficient (ADCmean) by diffusion-weighted magnetic resonance imaging (DWI) findings with prognostic factors in patients with squamous cell carcinoma (SCC) of primary cervical cancer. The pretreatment and posttreatment ADCmean of the primary tumor were examined for their correlations with the prognosis in 69 patients with SCC of primary cervical cancer by radiotherapy (RT) with or without concurrent chemotherapy (CCRT). The median disease-free survival (DFS) and overall survival (OS) times of patients were 20.97 and 23.47 months (follow-up periods for DFS and OS: 1-72 and 1-72 months). The DFS and OS rates of patients with low pretreatment and posttreatment ADCmean of the primary tumor were also significantly worse than those of patients exhibiting high pretreatment and posttreatment ADCmean of the primary tumor (DFS; P = 0.0130 and P < 0.0001, OS; P = 0.0010 and P < 0.0001). Multivariate analyses showed that low posttreatment ADCmean of the primary tumor was an independent prognostic factor for DFS and OS (P < 0.0001 and P < 0.0001). The low posttreatment ADCmean of the primary tumor is a useful clinical prognostic biomarker for recurrence and survival in patients with cervical cancer. The low posttreatment ADCmean of the primary tumor is a useful clinical prognostic biomarker for recurrence and survival in patients with cervical cancer.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to evaluate the effects of enoxaparin (ENO) and fondaparinux (FPX) on postoperative plasma D-dimer levels and risk factors associated with postoperative venous thromboembolism (VTE) and pulmonary thromboembolism (PTE) in patients with gynecologic cancer. For this study, 434 patients with gynecologic cancer were recruited and a surgical treatment strategy was employed. Plasma D-dimer levels were measured prior to surgery, as well as on a schedule up to 3 weeks postoperatively and again after day 28. Patients with clinical signs and elevation of the plasma D-dimer level underwent multidetector row computed tomography. The D-dimer value was significantly lower in patients with ENO or FPX on postoperative days 3-10 compared to patients with gynecologic cancers who were not receiving ENO or FPX. The D-dimer value was significantly lower in patients with FPX compared to patients with ENO on postoperative days 5-7. The D-dimer value on postoperative day 3, the use of erythropoiesis-stimulating agents (ESAs), advancing age and non-O blood group were independent risk factors for postoperative VTE. The D-dimer value on postoperative day 3 and the use of ESAs were independent risk factors for postoperative PTE. The postoperative D-dimer value was significantly lower in patients with gynecologic cancer who were administered ENO or FPX compared to patients were not administered either ENO or FPX. The use of ESAs and high plasma D-dimer levels on postoperative day 3 were independent risk factors for postoperative VTE and PTE.
Molecular and clinical oncology. 07/2013; 1(4):737-744.
[Show abstract][Hide abstract] ABSTRACT: Struma ovarii is a rare neoplasm that accounts for approximately 0.3% of ovarian tumors. Due to its ultrasound morphology, which is quite similar to that of malignant ovarian carcinoma, most struma ovarii cases are open operated with laparotomy rather than laparoscopy. We present 3 cases of struma ovarii, which were diagnosed preoperatively by imaging studies and removed by laparoscopic surgery. All patients were premenopausal women between ages 31‒50. The magnetic resonance imaging (MRI) findings were complex masses composed of multiple cysts and solid components with T2-hypointense regions as well as multiple T1-hyperintense cystic areas, findings that are typical for struma ovarii. A combination of plain computed tomography (CT), positron emission tomography (PET)-CT, and scintigraphy was useful for diagnosis. Laboratory examination revealed elevated serum thyroglobulin, which led to the diagnosis of struma ovarii. Laparoscopic surgeries were performed without rupturing the tumors. Although it has been difficult to differentiate between struma ovarii and malignant tumors by conventional methods, recently MRI techniques appear make it possible to diagnose struma ovarii preoperatively from the abovementioned imaging characteristic, together with laboratory data. As for treatment, we think laparoscopy could be successful for struma ovarii, but the surgeon must be careful not to rupture the tumor intra-abdominally in order to prevent dissemination, which could lead to malignancy.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to determine the incidence of increased levels of D-dimer and associated factors in preoperative patients with gynecological cancer. Furthermore, we determined the incidence and risk factors associated with preoperative venous thromboembolism (VTE). Overall, 456 patients with invasive gynecological cancer scheduled to undergo surgery were recruited. Preoperative plasma D-dimer levels were measured and patients whose plasma D-dimer concentration exceeded the pre-set cut-off value underwent computed tomography scanning. The incidence of elevated D-dimer and VTE was identified as significantly higher in patients with ovarian cancer. Multivariate analysis revealed that advanced age, low hemoglobin levels and elevated C-reactive protein (CRP) levels were independent factors for preoperative elevations in plasma D-dimer levels. Advanced age was an independent risk factor for preoperative VTE. Massive ascites and the presence of co-morbidities were independent risk factors for preoperative VTE in ovarian cancer. Advanced age and stage were independent risk factors for preoperative VTE in endometrial cancer. Advanced age was an independent risk factor for preoperative VTE in cervical cancer. Plasma D-dimer levels and the incidence of preoperative VTE were higher in patients with ovarian cancer compared with those with other gynecological cancers. Advanced age, low hemoglobin levels and elevated CRP levels were significant factors associated with elevated plasma D-dimer levels and age was an independent risk factor for preoperative VTE in gynecological cancer.
[Show abstract][Hide abstract] ABSTRACT: To examine the correlation between histopathology and magnetic resonance imaging (MRI) measured tumor size and define whether patients with Stage IB1 cervical cancer with an MRI-measured tumor size < or = 2 cm can be candidates for less-radical surgery.
The authors retrospectively reviewed 200 patients with Stage IB1 cervical cancer who underwent radical hysterectomy (class III) and pelvic lymphadenectomy. The largest diameter of the tumor was determined by MRI in 52 consecutive cases.
Regarding risk factors for parametrial involvement, only tumor size and age are known before definitive surgery without conization. Multivariate analysis of these risk factors revealed that both tumor size and old age were independently associated with parametrial involvement. Eighty-eight patients had a tumor size < or = 2 cm and an age < or = 50 years, two of which (2.3%) had parametrial involvement. In 52 consecutive patients, a significant correlation between histopathology- and MRI-measured tumor size was found (r = 0.787). Twenty-three patients had an MRI-measured tumor size < or = 2 cm, none of which had parametrial involvement.
Patients with Stage IB1 cervical cancer lesions with a tumor size < or = 2 cm measured by MRI and age < or = 50 years can be treated with less-radical surgery.
European journal of gynaecological oncology 01/2013; 34(1):39-41. · 0.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the changes in plasma soluble fibrin (SF) levels over time in gynecologic cancer patients following surgery. Furthermore, we examined the duration of the coagulation stage and determined a suitable duration for which thromboprophylaxis with anticoagulant agents should be administered. We retrospectively studied 311 patients with invasive gynecologic cancer who underwent surgery at Okayama University Hospital, Japan. The plasma SF levels were measured serially prior to the operation and on postoperative days 0, 1, 3, 5, 7, 10, 14, 21 and 28. The plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. The SF levels of patients with venous thromboembolism (VTE) were significantly different from those of VTE-negative patients on postoperative days 0-10. The SF levels on each day did not significantly differ between patients treated with chemical anticoagulants and those treated mechanically. The plasma SF levels were elevated (≥7.0 μg/ml) in 159 of the 311 patients (51.1%) on one of the days when these levels were measured. Among the patients with elevated plasma SF levels, 110 patients (69.2%) peaked on days 0-3 and only 9 patients (5.7%) peaked on days 21-28. Although only 1 of the 14 patients (7.1%) who showed peak levels on day 14 had undergone chemotherapy following surgery, 8 of the 9 patients (88.9%) whose levels peaked on days 21-28 had undergone chemotherapy following surgery (P= 0.0002). In conclusion, the plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. These levels peaked within 14 days of surgery in most cases. Therefore, chemical thromboprophylaxis may be administered for at least up to 14 days following surgery.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The purpose of this study was to investigate the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MR imaging and of the maximum standardized uptake value (SUVmax) derived from PET/CT imaging of the primary tumour in patients with endometrial cancer. METHODS: SUVmax reflects the highest tumour metabolism rate and ADCmin reflects the highest cellularity, and both parameters have been used for tumour grading and prediction of prognosis. The correlations between prognosis and SUVmax and ADCmin of the primary tumour were determined in 131 patients with endometrial cancer. The patients were divided into groups based on ADCmin and SUVmax cut-off values to predict recurrence and survival, which were derived from receiver operating characteristic curves. Disease-free survival (DFS) and overall survival (OS) of the groups were analysed using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test. RESULTS: The median DFS and OS times of all patients were 19.2 and 20.5 months (follow-up periods 1-70 months for both DFS and OS), respectively. Patients with high SUVmax had significantly lower DFS (P < 0.0001) and OS (P = 0.0092) than patients with low SUVmax. Multivariate analysis showed that high SUVmax was an independent prognostic factor for both DFS (P = 0.0161) and OS (P = 0.0232). CONCLUSION: The SUVmax of the primary tumour derived from PET/CT imaging could be an important prognostic indicator of recurrence and survival in patients with endometrial cancer.
European Journal of Nuclear Medicine 09/2012; · 4.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS: A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS: Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122×10(-3)mm(2)/s, 0.852×10(-3)mm(2)/s, 0.670×10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS: The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.
[Show abstract][Hide abstract] ABSTRACT: We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells, and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the anti-tumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.
Cancer biology & therapy 05/2012; 13(7):559-66. · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to determine possible factors associated with parametrial spread in patients with stage IB1 cervical cancer and define parameters associated with a low risk for parametrial spread, in order to identify candidates for less radical surgery.
We retrospectively reviewed 200 patients with stage IB1 cervical cancer who had undergone radical hysterectomy (class III) and pelvic lymphadenectomy.
Overall, 20 (10.0%) of the 200 patients revealed parametrial spread, of which 11 (55%) had only direct microscopic extension of the disease, 3 (15%) had only disease spread to parametrial lymph nodes, 1 (5%) had both direct microscopic extension and disease spread to parametrial lymph nodes, and 5 (25%) had only tumor emboli within the lymph vascular channels in the parametrial tissue. Elderly age, depth of invasion, tumor size, lymph vascular space invasion (LVSI), positive pelvic nodes, and ovarian metastasis were significantly associated with parametrial involvement. The multivariate analysis model included factors that could be determined by a cone biopsy and showed LVSI, deep stromal invasion, and elderly age to be the independent predictors of parametrial involvement. Ninety-one patients had a depth of invasion of ≤10 mm and no LVSI, of which only 1 (1.1%) had parametrial involvement. When patients aged ≤50 years were further stratified into those with a depth of invasion of ≤10 mm and no LVSI, parametrial involvement was found to be 0.0% (0/68).
Patients with a tumor depth of invasion of ≤10 mm, no LVSI, and aged ≤50 years, could be considered for less radical surgery such as modified radical hysterectomy or simple hysterectomy with pelvic lymphadenectomy.
[Show abstract][Hide abstract] ABSTRACT: Although anthracyclines are considered as being among the most potent chemotherapeutic agents for endometrial carcinoma, the majority of institutions in Japan prefer a combination of paclitaxel and carboplatin (TC) for treating this disease. We retrospectively evaluated the efficacy and feasibility of combined paclitaxel, pirarubicin, and carboplatin (TPC) therapy for endometrial carcinoma.
Thirty-nine patients with high/intermediate postoperative recurrence risks or with advanced disease received combination chemotherapy consisting of paclitaxel (150 mg/m(2)), pirarubicin (35 mg/m(2)), and carboplatin [area under the concentration time curve (AUC = 4)] from 2001 to 2006 at Okayama University Hospital. Treatment cycles were repeated every 3 weeks, and three to nine cycles were administered according to patient risk.
The 1-year overall survival (OS) and progression-free survival (PFS) rates were 94.9% and 84.6%, respectively, and the 3-year OS and PFS rate was 81.3%. Hematologic toxicities >grade 3 were: anemia 30.8%; leukopenia 84.6%; thrombocytopenia 20.5%. Neutropenia was common, and administration of granulocyte colony-stimulating factor (G-CSF) was necessary in 87.9% of treatment courses. Although grade 3 or 4 neutropenia was unavoidable, we could administer TPC therapy safely and without delay with G-CSF support. Gastrointestinal and neurological toxicity were less severe and less frequent compared with TC, and no cardiac toxicity was observed.
The 3-year PFS and OS rates even in high-risk patients were satisfactory, and we confirmed the feasibility of using this regimen for treating endometrial carcinoma.
International Journal of Clinical Oncology 10/2010; 15(5):476-83. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to evaluate whether early postoperative D-dimer levels and certain pre-, intra-, and postoperative parameters can be used to predict venous thromboembolism (VTE) in gynecologic cancer patients. Materials and methods: We prospectively evaluated 267 gynecologic cancer patients who underwent surgery at our institution. The plasma D-dimer level was measured serially before the operation and on certain postoperative days. After the operation, primary screening for VTE was undertaken by meticulous examination for clinical signs and elevation of the plasma D-dimer level. Seventy-five patients underwent multidetector row computed tomography and were subjected to further investigations.
VTE was detected in 21 of the 75 patients. There were significant differences in the D-dimer value between VTE-positive and VTE-negative patients on postoperative days 3, 5, and 7. The optimal cut-off value for the postoperative D-dimer level was determined as 5 mug/ml on day 3. Logistic regression multivariate analysis revealed that high D-dimer values on postoperative day 3, the use of recombinant human erythropoietin (rHuEPO), and non-O blood group were independent risk factors for postoperative VTE.
High plasma D-dimer level on postoperative day 3, the use of rHuEPO, and non-O blood group were independent risk factors for postoperative VTE.
Annals of Oncology 08/2010; 21(8):1651-6. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few reports delineate the pharmacokinetics of combination chemotherapy with paclitaxel and carboplatin in hemodialysis (HD) patients with epithelial ovarian cancer. However, the optimal carboplatin dose and the timing of HD have yet to be elucidated. We presented a case of an advanced-stage epithelial ovarian cancer patient with chronic renal failure requiring HD. After 4 courses of combination chemotherapy consisting of paclitaxel and carboplatin, a partial response was obtained; therefore, she underwent interval debulking surgery. Paclitaxel was administered for 3 h at a dose of 150 mg/m(2), and carboplatin was administered for 1 h at a dose of 4-7 area under the concentration/time curve (AUC), which was calculated by the Calvert formula. HD was initiated 24 h after the start of administration of carboplatin and performed for a period of 3 h. Pharmacokinetic studies showed that the AUCs of free platinum and paclitaxel were 3.48-5.55 mg·min/ml and 13.5 μg·h/ml, respectively. Combination chemotherapy consisting of paclitaxel and carboplatin is a feasible approach to improving the treatment outcome of epithelial ovarian cancer patients with chronic renal failure requiring HD. The measurement of free platinum is useful in determining the optimal dose of carboplatin in order to obtain an adequate AUC. Determining the dose of carboplatin according to the Calvert formula and initiating HD after 24 h would ensure a favorable therapeutic effect with limited side effects.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to identify prognostic factors and patterns of recurrence in patients with stage IB-IIB cervical adenocarcinoma who had undergone radical surgery and to compare these patterns with those observed in squamous cell carcinoma (SCC) patients.
We retrospectively reviewed 303 patients (97 with adenocarcinoma and 206 with SCC) with stage IB-IIB cervical cancer who had undergone radical hysterectomy and pelvic lymphadenectomy.
In the case of the adenocarcinoma patients, lymph node metastasis and parametrial invasion were independent indicators of disease-free survival, whereas lymph node metastasis was the only independent prognostic factor for the overall survival of the patients. The sites of recurrence did not significantly differ between the adenocarcinoma and SCC patients. In parametrium-positive patients, adenocarcinoma was found to be an independent prognostic factor for disease-free survival. In patients with positive pelvic lymph node, adenocarcinoma was found to be an independent prognostic factor for both disease-free and overall survival.
Adenocarcinoma was found to be an independent prognostic factor for survival in patients with positive pelvic node or parametrial extension. Furthermore, the patterns of recurrence did not differ significantly between the adenocarcinoma and SCC patients.
Journal of Surgical Oncology 04/2010; 101(5):413-7. · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proteoglycans are ubiquitous components of the extracellular matrix and cell surface, and may mediate tumor progression and metastasis. The aim of this study was to evaluate the expression of syndecan-1 and versican in epithelial ovarian cancer. We immunohistochemically evaluated the expression of syndecan-1 and versican in 111 patients with epithelial ovarian cancer, and analyzed the correlation of this expression with various observed clinicopathological features, including patient outcome. There is a significant correlation between primary and metastatic sites with respect to syndecan-1 and versican expression. Epithelial syndecan-1 expression was significantly lower in patients with advanced disease. Epithelial versican expression was significantly higher in patients with early disease, especially in clear cell adenocarcinoma patients. Stromal syndecan-1 and versican expression was significantly higher in patients with advanced disease. Multivariate analysis showed that negative epithelial syndecan-1 expression was an independent prognostic factor for progression-free survival. Stromal syndecan-1 and versican co-expression was of borderline significance for progression-free and overall survival. Loss of epithelial syndecan-1 expression and induction of stromal syndecan-1 and versican expression may be associated with tumor progression in epithelial ovarian cancer. Syndecan-1 and versican expression status can serve as an indicator of prognosis in patients with epithelial ovarian cancer.
[Show abstract][Hide abstract] ABSTRACT: Endometrial carcinomas producing α-fetoprotein (AFP) are extremely rare. We report a case of AFP-producing, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. A 59-year-old multiparous woman presented with abdominal swelling. The serum level of AFP was 1292.8 ng/ml. Magnetic resonance images of the pelvis showed a markedly enlarged uterus, with a tumor growing exophytically within the endometrial cavity. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The histopathological examination demonstrated a Stage IIA, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. The endometrioid adenocarcinoma cells were partly positive for AFP immunoreactivity. The patient received adjuvant chemotherapy and was disease-free 60 months after the operation. This case confirms the existence of AFP-producing endometrioid adenocarcinomas without hepatoid features.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to evaluate the efficacy of diagnostic laser conization and the obstetric outcomes of patients undergoing diagnostic laser conization during pregnancy.
The study population consisted of a consecutive series of 47 patients who presented with histologically proven carcinoma in situ microinvasive carcinoma and were treated with laser conization during pregnancy.
Diagnostic laser conization was performed at 3-28 weeks (median, 13 weeks) of gestation. Intraoperative blood loss of > 500 ml was observed in two cases (4.3%); however, hemotransfusion was not required in either case. In the early postoperative period, two miscarriages due to preterm premature rupture of the membrane were observed. In the late postoperative period, one spontaneous abortion, three preterm deliveries, and one neonatal death were observed. All the poor obstetric outcomes were observed in the case of patients who underwent conization in the first trimester. The pathology report for the laser conization revealed that two patients (4.3%) had invasive carcinoma. Of the 47 patients, 29 (61.7%) had positive cervical margin, and 13 required postpartum surgical intervention. All patients treated were disease-free at the time of the subsequent follow-up.
The results of the present study suggest that laser conization in pregnant patients is feasible and is comparable to cold-knife conization and loop electrosurgical excision procedures with regard to the rates of complication and obstetric outcomes. Furthermore, they indicate that the optimal time for conization is probably the second trimester.
European journal of gynaecological oncology 01/2010; 31(4):399-401. · 0.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The insulin-like growth factor I receptor (IGF-IR) is exceptionally overexpressed in many cervical-cancer-derived cell lines. It is postulated that a decrease of p53 protein levels due to human papillomavirus (HPV) infection may contribute to the up-regulation of IGF-IR expression in cervical cancer cells because transcription of IGF-IR is strictly down-regulated by p53. To evaluate this fact in clinical cervical cancer specimens, we checked the expression levels and activated status of IGF-IR by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens obtained by conization or hysterectomy were stained with anti-IGF-IR and with an antibody recognizing phosphorylated tyrosine at its c-terminus. The expression levels of IGF-IR were significantly high in cervical intraepithelial neoplasia (CIN) III and invasive cancer specimens. Phosphorylation of IGF-IR was promoted in all CIN and invasive cancer specimens, and its intensity was related to the promotion of lesions. Interestingly, IGF-IR overexpression was missing in the basal layer of CIN I and II lesions, whereas it was evenly distributed in CIN III and invasive cancer lesions. This IGF-IR overexpression pattern may be utilized in the diagnosis of HPV infection status in CIN lesions.
[Show abstract][Hide abstract] ABSTRACT: Cisplatin and ifosfamide are considered among the most active drugs in both neoadjuvant and salvage treatments for patients with cervical cancer. Nedaplatin is an analog of cisplatin and it exhibits lesser nephrotoxicity, neurotoxicity, and gastrointestinal toxicity than cisplatin. This study aimed to determine the recommended dosage of nedaplatin plus ifosfamide chemoradiotherapy for advanced squamous cell carcinoma (SCC) of the uterine cervix. Beginning with a dose of 65 mg/m(2), nedaplatin (day 1) combined with ifosfamide 1 g/m(2) (days 1-5) was designed to be administered for three cycles (minimum: two cycles); its dose was gradually escalated up to 80 mg/m(2). Dose-limiting toxicity (DLT) was defined as a more than 7-day delay in the planned radiation therapy and/or planned chemotherapy (prior to the completion of two cycles) due to toxicity. Chemotherapy was not interrupted prior to the completion of two cycles in any patients. Of the 12 patients, 11 received three cycles of chemotherapy. DLT did not occur in any patient. We confirmed a clinical complete response (CR) in ten and partial response (PR) in two patients. The median follow-up period was 39 months (range: 18-57 months). Ten patients (83%) were alive and disease free, one patient was alive with disease, and only one patient died due to the disease. Nedaplatin and ifosfamide combination chemotherapy is a feasible and active chemoradiation strategy for patients with advanced SCC of the uterine cervix. With the ifosfamide dose fixed to 1 g/m(2), the recommended nedaplatin dosage was determined to be 80 mg/m(2) to be administered for three cycles.
International Journal of Gynecological Cancer 03/2008; 18(6):1300-4. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nedaplatin is an analog of cisplatin that was developed in Japan, and it exhibits less nephrotoxicity, neurotoxicity, and gastrointestinal toxicity than cisplatin. This study aimed to determine the recommended dose of weekly nedaplatin chemoradiotherapy in high-risk patients following radical surgery. Fifteen patients who required postoperative pelvic radiotherapy after radical surgery for cervical cancer were enrolled in the present study. Nedaplatin was designed to be administered for eight cycles (minimum five cycles) beginning at a weekly dose of 22.5 mg/m(2) and then escalating to 25, 27.5, and then to 30 mg/m(2). Dose-limiting toxicity was defined as a more than 7-day delay in the planned radiation therapy and/or planned chemotherapy (prior to the completion of five cycles) due to toxicity. Nedaplatin administration was interrupted prior to the completion of five cycles in one of six patients at a dose of 27.5 mg/m(2). A more than 7-day delay in the planned radiation therapy did not occur in any patient. Nedaplatin at a dose of 30 mg/m(2) was safely administered, and two of three patients could receive the planned chemotherapy consisting of eight cycles of weekly nedaplatin. Our recommended weekly nedaplatin dose was determined to be 30 mg/m(2) administered for more than five cycles and up to eight cycles if possible. Weekly administration of nedaplatin may be more tolerable and less toxic than weekly administration of cisplatin.
International Journal of Gynecological Cancer 12/2007; 18(5):1037-41. · 1.94 Impact Factor