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Objective: The effectiveness of paclitaxel-cisplatin-ifosfamide triplet regimen (TIP) was reported to be superior to that of paclitaxel-cisplatin doublet. However, the efficacy of paclitaxel-cisplatin-bevacizumab triplet (TPA) and TIP has not been compared. Here, we compared the efficacy and safety of TIP and TPA in patients with metastatic, recurrent, or persistent cervical cancer., Methods: We retrospectively reviewed the medical records of patients with recurrent, persistent, or metastatic cervical cancer who were at the Samsung Medical Center, Seoul, Korea between January 2005 and September 2018. Of the 161 patients included in the study, 92 had received TIP and 71 had received TPA. For the study, we compared the response rates, progression-free survival (PFS), overall survival (OS), and safety in the 2 treatment groups., Results: The response rates of patients who received TIP and TPA were comparable (64.1% vs 73.2%, P = 0.239). Histology (squamous vs nonsquamous) was the only prognostic factor that affected the response to therapy (odds ratio, 0.259; 95% confidence interval [CI], 0.119-0.562; P = 0.001). The PFS after TIP and TPA treatment was similar: 12.0 months (95%CI, 10.26-13.74) vs 11.5 months (95%CI, 10.18-12.83), respectively. In a Cox proportional hazard model, objective response to therapies was the only independent prognostic factor for both PFS and OS. However, different types of therapy (TIP vs TPA) did not affect the oncological outcomes for either PFS or OS. Although hematologic toxicity was significantly higher in the TIP-treated group than in the TPA-treated group, both regimens were safe and well-tolerated., Conclusions: The effectiveness and safety of TIP was comparable to TPA in terms of response rates, survival, and adverse effects. TIP could be an effective alternative in the treatment of cervical cancer when TPA is contraindicated or unaffordable., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Paclitaxel/ifosfamide/cisplatin triplet has shown a higher response rate than paclitaxel/cisplatin doublet, but the toxicity profile hindered the use of the triplet regimen. In this study, we adjusted the dosage of the triplet regimen and introduced carboplatin in cisplatin-intolerable patients. We tested the efficacy and toxicity of the modified triplet regimen in patients with recurrent or persistent cervical cancer., Materials and Methods: We retrospectively reviewed the medical records of patients with recurrent or persistent cervical cancer who were treated between 2003 and 2015 at Samsung Medical Center. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity of paclitaxel/ifosfamide/platinum (TIP) and paclitaxel/platinum (TP) were compared., Results: The overall response rate of TIP was significantly higher than that of TP (52.7% vs 36.4%, P = 0.031). In the TP group, response rate was higher in patients with progression-free interval longer than 12 months (P = 0.028) and those with squamous cell histology (P = 0.028). In TIP group, patients with older than 50 years (P = 0.017), progression-free interval longer than 12 months (P = 0.046), and squamous cell carcinoma histology (P < 0.001) showed higher response rates; but TIP showed higher response on all occasions. Median OS and median PFS were similar for TP and TIP (OS, 22.43 months vs 18.5 months, P = 0.44; PFS, 6.37 months vs 8.3 months, P = 0.48)., Conclusions: Paclitaxel/ifosfamide/platinum showed a higher response rate than TP in patients with recurrent cervical cancer without an increase in severe complications. Considering the high response rate, TIP may be an option for persistent or recurrent cervical cancer.

Clinical practice guidelines for gynecologic cancers have been developed by academic society from several countries. Each guideline reflected their own insurance system and unique medical environment, based on the published evidence. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to develop the third edition of the guidelines in an advanced format based on evidence-based medicine, embracing up-to-date clinical trials and qualified Korean data. These guidelines cover strategies for diagnosis and treatment of primary and recurrent cervical cancer. The committee members and many gynecologic oncologists derived key questions through discussions, and a number of relevant scientific literature were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, along with the details. The objective of these practice guidelines is to establish standard policies on issues in clinical practice related to the management in cervical cancer based on the results in published papers to date and the consensus of experts as a KSGO Consensus Statement., Competing Interests: Jae-Weon Kim, Myong Cheol Lim, Jeong-Yeol Park, and Seung-Hyuk Shim serve as editors of the Journal of Gynecologic Oncology (JGO), but have no role in the decision to publish this article. No other conflict of interest relevant to this article was reported., (Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objective: The aim of this study was to analyse patterns and timing of recurrence and their association with clinical outcomes in recurrent epithelial ovarian cancer (EOC) patients with no gross residual disease after primary debulking surgery (PDS)., Methods: This study was conducted on 303 EOC patients with no residual disease after PDS who were treated at the Samsung Medical Center from 2002 to 2012. By reviewing electronic medical records, information on date of clinical/pathological recurrence and pattern of disease presentation for each relapse were retrieved., Results: Within a median follow-up of 53 months (range 3-156), 88 recurrences (29.0%) and 28 cancer-related deaths (9.2%) were observed. Most of the recurrences were distant, discrete and transcoelomic. After complete cytoreduction, the initial stage was associated with location of recurrence, but not with recurrence patterns. Complete cytoreduction reduced the number of recurrences, but it did not affect timing of recurrence. In multivariate analysis for overall survival (OS), patients with distant recurrence, diffuse carcinomatosis and mixed spread pattern of transcoelomic, lymphatic and haematogenous recurrence were found to have higher risk., Conclusions: We found that timing of recurrence was not affected by complete cytoreduction. Location, type and pattern of recurrence were also significant prognostic factors for OS, in addition to known prognostic predictors such as platinum sensitivity., (© 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To investigate the impact of pelvic and para-aortic lymphadenectomy during primary debulking surgery (PDS) on recurrence pattern and survival after recurrence in patients with advanced epithelial ovarian cancer (EOC) without suspected lymph node (LN) metastasis in preoperative imaging studies and intraoperative findings., Methods: A retrospective review of patients with FIGO stage III and IV EOC without suspected lymph node metastasis was performed. Patients with stage III EOC due to LN metastasis without peritoneal disease were excluded from this study. Survival comparisons for progression-free survival (PFS), overall survival (OS), and survival after recurrence were performed between patients with or without lymphadenectomy., Results: Of the 261 EOC patients fulfilling inclusion criteria, 194 (74.3%) experienced relapse and a further 132 (50.6%) died within a median follow-up period of 48months (range, 6-139months). Patterns of recurrence and CA-125 level at recurrence were not different between patients with lymphadenectomy and without lymphadenectomy; however, patients with lymphadenectomy showed longer survival after recurrence than those without lymphadenectomy (43 vs. 32months, p=0.013). This difference was pronounced in the group with residual tumor <1cm (48 vs. 30months, p=0.010). The survival advantage of lymphadenectomy after recurrence remained significant in multivariate analysis (HR 0.57, 95% CI 0.38-0.84, p=0.005)., Conclusions: Lymphadenectomy during PDS was associated with longer survival, especially survival after recurrence. The underlying mechanism should be elucidated in future studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to compare survival outcomes in two groups of patients with recurrent epithelial ovarian cancer (EOC) with initial recurrence detection by cancer antigen 125 (CA-125) elevation or imaging, and underwent secondary cytoreductive surgery (SCS)., Methods: A retrospective review of the medical records was performed on 99 recurrent EOC patients who underwent SCS at the Samsung Medical Center between January 2002 and December 2013. For follow-up after primary treatment, patients were routinely assessed by CA-125 levels every 3 months and computed tomography (CT) scan (or magnetic resonance imaging [MRI]) every 6 months for first 3 years, and by CA-125 every 6 months and CT scan (or MRI) every 12 months thereafter., Results: The first recurrence was initially identified by either CA-125 elevation (n=41, 41.4%) or by imaging study (n=58, 58.6%). None of the patients showed the symptoms as initial sign of recurrence. There were higher percentages of extra-pelvic recurrence (87.8%) and multiple recurrences (78.0%) in the group diagnosed by CA-125 elevation. The proportion of no residual disease after SCS was comparably lower in the CA-125 group (22.0% vs. 72.4%). There were 19 cancer-associated deaths (19.2%) within a median follow-up period of 67 months. The group diagnosed by imaging had better overall survival from initial diagnosis (OS1), overall survival after SCS (OS2), progression-free survival after the initial treatment (PFS1) and progression-free survival after SCS compared to those of the CA-125 group (PFS2)., Conclusion: EOC patients with recurrence initially detected by imaging study showed better survival outcomes than patients diagnosed by CA-125 elevation.

Objective: To assess the feasibility of laparoscopic cytoreduction in patients with localized recurrent epithelial ovarian cancer (EOC) by comparing its outcomes to those of laparotomy., Methods: We performed retrospective analysis in 79 EOC patients who had a localized single recurrent site, as demonstrated by computed tomography (CT) scan, magnetic resonance imaging, or positron emission tomography/CT scan; had no ascites; were disease-free for 12 or more months prior; and who had undergone secondary cytoreduction (laparoscopy in 31 patients, laparotomy in 48 patients) at Samsung Medical Center between 2002 and 2013. By reviewing the electronic medical records, we investigated the patients' baseline characteristics, surgical characteristics, and surgical outcomes., Results: There were no statistically significant differences between laparoscopy and laparotomy patients in terms of age, body mass index, cancer antigen 125 level, tumor type, initial stage, grade, recurrence site, type of procedures used in the secondary cytoreduction, adjuvant chemotherapy, and disease-free interval from the previous treatment. With regards to surgical outcomes, reduced operating time, shorter hospital stay, and less estimated blood loss were achieved in the laparoscopy group. Complete debulking was achieved in all cases in the laparoscopy group., Conclusion: The laparoscopic approach is feasible without compromising morbidity and survival in selected groups of patients with recurrent EOC. The laparoscopic approach can be a possible treatment option for recurrent EOC.

Objective: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC., Methods: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated., Results: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease., Conclusion: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Objective: This study aimed to compare the laparoscopic-assisted radical vaginal trachelectomy (LARVT) and laparoscopic radical trachelectomy (LRT) surgical approaches and provide outcome data on patients who have undergone radical trachelectomy., Methods: We identified patients who had undergone LARVT or LRT at Samsung Medical Center between January 2005 and March 2013., Results: A total of 38 patients were identified, and 21 patients had undergone LARVT, whereas 17 patients had undergone LRT. The median age was 32 years for both groups. Most of the patients had a squamous cell carcinoma (68.4%) and International Federation of Gynecology and Obstetrics stage IB1 disease (76.3%). Twenty (52.6%) of 38 patients had tumor size greater than 2 cm. There were no significant differences between groups in the baseline characteristics except for the tumor size. Patients undergoing LRT had significantly larger tumor size than patients undergoing LARVT (median tumor size, 2.7 cm [range, 1.2-3.7] vs 2.1 cm [range, 0.4-3.0], P = 0.032). Perioperative outcomes were similar between groups except for the decline of hemoglobin after surgery. The median decline of hemoglobin indicating blood loss was significantly smaller in the LRT group than in the LARVT group (1.8 g/dL [range, 0.5-3.5] vs 2.6 g/dL [range, 0.7-6.2], P = 0.017). Intraoperative complications occurred in 2 patients (9.5%, 2/21) in LARVT group. Although 52.6% of tumors were larger than 2 cm, recurrence occurred only in 3 (7.9%) patients who underwent LARVT., Conclusions: The study shows the feasibility of LRT, with the advantage of reduced blood loss. The LRT could be an alternative option for patients with large tumors. Further researches are needed to investigate the long-term outcomes.

Objective: The aim of this study was to assess the relative incidences of cervical adenocarcinoma in situ (AIS) and squamous cell carcinoma in situ (sCIS) and to determine the effect of coexisting squamous cell lesions on prognosis in patients with cervical AIS., Study Design: We performed a retrospective review of patients diagnosed with AIS or sCIS who underwent cervical conization at a University hospital between 2000 and 2011., Results: A total of 1184 patients with cervical carcinoma in situ were included. The ratio of sCIS to AIS was 16:1. Among 71 patients with AIS, AIS with coexisting squamous cell lesions and AIS alone were detected in 41 patients (58%) and 30 patients (42%), respectively. During the median follow-up of 57.1 months, 5 episodes of AIS recurrences and one episode of invasive recurrence occurred. The recurrence rate was significantly higher in patients with AIS alone than in patients with AIS and coexisting squamous cell lesions (17% versus 2%; P=0.043)., Conclusion: These results suggest that patients with cervical AIS and coexisting squamous cell lesions have a more favorable prognosis than patients with AIS alone., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Borderline ovarian tumor (BOT) is uncommon in women with advanced age. The authors investigated the characteristics and treatment outcomes of women with BOT ≥ 65 years of age., Study Design: A hospital-based tumor registry was used to identify retrospectively patients with BOT who were treated between 1996 and 2011. Patients were divided into two cohorts: women aged <65 years and women aged ≥ 65 years. Recurrence and survival was examined using the Kaplan-Meier method. Multivariate Cox proportional hazards model was used to estimate hazard ratios with 95% confidence intervals (95% CI)., Results: In total, 364 patients were identified, including 326 patients aged <65 years and 38 patients aged ≥ 65 years. The elderly patients had more comorbidities (P < 0.001), larger tumor size at diagnosis (P = 0.001), more perioperative complications (P = 0.001), and longer postoperative hospital stay (P < 0.001). In a multivariate model, the hazard ratios for recurrence and disease-related death in patients aged ≥ 65 years were 2.53 (95% CI, 1.03-6.23) and 7.66 (95% CI, 1.09-53.95), respectively., Conclusions: Characteristics and survival of patients with BOTs aged ≥ 65 years differ distinctly from those of patients aged <65 years. Old age was an independent poor prognostic factor of recurrence and disease-related death., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Tumor volume is a significant prognostic factor of cervical cancer. It is still unknown about outcome of biopsy-proven IB1 cervical cancer, which is invisible on preoperative magnetic resonance imaging (MRI). The aim was to evaluate retrospectively the postoperative outcomes of MR-invisible stage IB1 cervical cancers., Study Design: Between January 2001 and December 2007, we reviewed the medical records of 86 patients with biopsy-proven IB1 cervical cancer that was invisible on MRI. During the same period, we also reviewed the medical records of 260 patients with biopsy-proven IB1 cervical cancer that was visible on MRI. Both of these cancer groups were treated with radical hysterectomy and lymph node dissection. MR-invisible and MR-visible IB1 cancers were compared in terms of pathologic parameters and long-term survival rate., Results: The median sizes and depths of stromal invasion of MR-invisible vs MR-visible IB1 cancers were 4.5 ± 7.1 mm and 33.3% ± 20.1% vs 30 ± 14 mm and 66.7% ± 26.6%, respectively (P = .000). The incidences of lymph node metastasis, parametrial invasion, and lymphovascular invasion were 1.1% (1/86 cases) and 18.8% (49/260 cases; P = .000; odds ratio, 19.7), 0% (0/86 cases) and 6.5% (17/260 cases; P = .009; odds ratio, 12.4), and 4.7% (4/86 cases) and 26.9% (70/260 cases; P = .000; odds ratio, 7.6) in the MR-invisible and MR-visible IB1 cancers, respectively. Recurrence-free and overall 5-year survival rates of MR-invisible vs MR-visible IB1 cancers were 98.8% (85/86 cases) vs 91.2% (237/260 cases) and 100% (86/86 cases) vs 95.8% (249/260 cases), respectively (P = .011 and .045)., Conclusion: MR-invisible IB1 cancer provides better postoperative outcomes than MR-visible IB1 cancer because of the much lower tumor burden., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: Recurrence is the major cause of death in early cervical cancer. We compared the prediction powers for disease recurrence between the gene set prognostic model and the clinical prognostic model., Materials and Methods: A gene set model to predict disease free survival was developed using the cDNA-mediated annealing, selection, extension, and ligation (DASL) assay data set from a cohort of early cervical cancer patients who had been treated with radical surgery with or without adjuvant therapy. A clinical prediction model was also developed using the same cohort, and the ability of predicting recurrence from each model was compared., Results: Adequate DASL assay profiles were obtained from 300 patients, and we selected 12 genes for the gene set model. When patients were categorized as having a low or high risk by the prognostic score, the Kaplan-Meier curve showed significantly different recurrence rates between the two groups. The clinical model was developed using FIGO stage and post-surgical pathological findings. In multivariate Cox regression analysis of prognostic models, the gene set prognostic model showed a higher hazard ratio than that of the clinical prognostic model., Conclusions: The genetic quantitative approach may be better in predicting recurrence in early cervical cancer patients., (© 2013 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to describe the clinical characteristics and to assess the contributing factors in patients developing bone metastasis in uterine cervical cancer., Methods: Two thousand thirteen patients had a diagnosis of uterine cervical cancer at Samsung Medical Center between June 1994 and December 2011. During the study period, 105 patients with bone metastasis were identified, and their clinicopathologic data were investigated retrospectively., Results: Among 105 patients with bone metastasis, 14 patients were excluded and 91 patients were evaluable. The median bone metastasis-free survival was 27 months (range, 0-279 months).The time to bone metastasis was significantly shorter in patients with adenocarcinoma than in patients with squamous cell carcinoma (median duration, 12 vs 29 months; P = 0.016). In addition, it was shorter in patients with stage IIB to stage IV disease than in those with stage I to stage IIA disease (15 vs 22 months; P = 0.02). The median survival after bone metastasis was 10 months, longer in the patients who received radiotherapy (± chemotherapy) than in the patients who received chemotherapy alone as a salvage therapy (12 vs 7 months; P = 0.01). Initial stage, number of bone metastases, location of involved bone, and coexisting metastatic lesion were not associated with the overall survival of the patients., Conclusions: Our study demonstrates that adenocarcinoma, advanced stage (IIB-IV) and initial multiple bone metastases contribute to earlier bone metastasis. Once bone metastasis was recognized, the survival of these patients was poor and no factors were identified to predict survival of those patients.

Introduction: The purpose to this study was to compare the clinicopathologic characteristics and prognosis of patients with serous stage I borderline ovarian tumors (BOTs) to patients with mucinous stage I BOTs., Methods: This was a retrospective cohort series of patients with stage I BOTs diagnosed and treated between 1995 and 2009 at a single institution. The records were analyzed for patients' clinicopathologic information. The recurrence rates were compared using the Kaplan-Meier method., Results: During the study period, 198 patients (73.6%) with mucinous BOTs and 71 patients (26.4%) with serous BOTs were identified. Patients with serous tumors tended to be asymptomatic (53.5%) and frequently had elevated CA-125 levels and positive results from peritoneal cytology. Conversely, mucinous tumors were more related to the presence of symptoms (70.7%), elevated CA-19-9 levels, and pseudomyxoma and were larger tumors with a mean size of 15.6 cm. After a median follow-up of 56.5 months, 15 patients had developed 16 recurrences. Among these, 14 borderline recurrences developed in 6 patients with mucinous tumors and in 7 patients with serous tumors, and 2 invasive recurrences developed in only patients with mucinous tumors. No difference in recurrence rate between mucinous and serous tumors was observed. In addition, no disease-related death occurred., Conclusions: Our study found that, although distinct differences in clinical and pathologic characteristics between stage I mucinous and serous BOTs are seen, result from tumor histology was not associated with disease prognosis.

Objective: The purpose of this study was to compare the patterns of recurrence in patients with risk of lymph node (LN) metastasis or recurrence according to the extent of lymphadenectomy (LND)., Methods: We selected 257 patients with risk of LN metastasis or recurrence who underwent definitive surgery as the first treatment between 1995 and 2009. These patients underwent hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy (PLND) with or without para-aortic lymphadenectomy (PALND). We identified patients with recurrence and evaluated the patterns of recurrence according to the type of LND., Results: Among the 257 patients, 164 patients had systematic PLND only, and 93 patients had PLND with PALND. Regarding LN metastasis in PLND+PALND group, approximately 9.7% patients had involvement of para-aortic nodes. Thirty-six (14%) of the 257 patients showed recurrence. The rate of extrapelvic recurrence was significantly higher in the PLND group compared with the PLND+PALND group (96.0% vs 36.4%, respectively; P < 0.001). Using multivariate analysis, extent of LND was significantly related to extrapelvic recurrence (P = 0.004)., Conclusions: The incidence of extrapelvic recurrence was significantly higher in the PLND group than in the PLND+PALND group, which suggests that PALND decreases the risk of extrapelvic recurrence.

Objective: To evaluate the oncologic safety and reproductive outcomes in patients with advanced-stage borderline ovarian tumors (BOTs)., Study Design: The medical records of patients with advanced-stage BOTs who were treated between 1997 and 2009 were reviewed retrospectively. Reproductive outcomes were assessed by telephone interviews., Results: Six (24%) and 19 patients (76%) had stages II and III disease, respectively. Twenty patients (80%) were treated by radical surgery and five patients (20%) underwent fertility-sparing surgery. Five patients (20%) had invasive implants and 20 patients (80%) had non-invasive implants. The median follow-up time was 71.4 months (range, 10-135 months). Four patients relapsed after a median interval of 40 months (range, 16-77 months) following primary treatment. Of these four patients, two who initially had invasive implants relapsed in the form of invasive ovarian carcinoma. Patients with invasive implants (2 of 5 [40%]) tend to relapse more frequently than patients with non-invasive implants (2 of 20 [10%]). Among five women who underwent fertility-sparing surgery, four attempted to conceive and five singleton pregnancies occurred., Conclusion: Patients with advanced-stage BOTs with non-invasive implants have an excellent prognosis. Fertility-sparing surgery should be considered if there are no invasive implants. Indeed, reproductive outcomes after fertility-sparing surgery with non-invasive implants are promising., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: This retrospective study evaluates the efficacy and toxicity of topotecan, followed by cisplatin, in patients with persistent or recurrent cervical cancer., Methods: Twenty-four patients were included in the study. Ninety-two cycles of chemotherapy were administered during the study period. Topotecan (0.75 mg/m(2)) was administered as a 30-minute infusion on 3 consecutive days, and cisplatin was given intravenously at a dose of 50 mg/m(2) over 1h on day 3 of every third week., Results: The median number of cycles administered was 3, with a range of 1-8 cycles per patient. There were 4 (16.7%) complete responses, 3 (12.5%) partial responses, and 5 (20.8%) stable disease. All of the patients with a complete response had received palliative radiation or surgery for pain or an isolated solitary recurrence prior to chemotherapy. There were no treatment delays of >7 days per cycle due to hematologic toxicity. There were 59 days of delay (average, 0.6 days per cycle) in 21 of 92 (22.8%) cycles and two episodes of dose reduction (cisplatin, 50% reduction) in 2 patients due to low creatinine clearance (30-60 mL/min). Overall, grade 3/4 anemia, thrombocytopenia, and neutropenia were experienced in 13.1%, 1.1%, and 18.5% of the courses, or 33.4%, 4.2%, and 45.8% of the patients, respectively., Conclusion: Combination chemotherapy, consisting of topotecan on days 1-3 and cisplatin on day 3, showed a relatively low rate of hematologic toxicity, as compared with the regimen of topotecan on days 1-3 and cisplatin on day 1, as used in previous studies., (Copyright © 2010. Published by Elsevier Inc.)

Objective: The aim of this trial was to investigate the efficacy and toxicity of a relative high-dose of topotecan combined with carboplatin in recurrent or persistent epithelial ovarian cancer (EOC)., Methods: Patients participating in this phase II trial received topotecan at a dose of 1.0 mg/m(2)/day intravenously (IV) on days 1 to 5 in combination with carboplatin AUC 5 IV on day 5, every 21 days. The primary outcome was response rate (RR) and the toxicity. The secondary measurements were duration of response, time to progression (TTP) and overall survival (OS)., Results: Fifty-nine patients entered the study and 53 were assessable for response. For this study, 260 courses of topotecan and carboplatin were given (median, 4 per patient; range, 1-8). The overall RR was 26.4%. The median duration of response and TTP were 7 and 6 months, respectively. The median OS was 19 months with a median follow-up period of 14 months. Initial platinum sensitivity and treatment free interval (TFI) >or=6 months were associated with RR and OS. In the platinum-sensitive group, RR and OS were 40.0% and 25 months, whereas in the platinum-resistant group, these were 8.7% and 11 months, respectively. Grade 4 neutropenia occurred in 40.7% of the patients, and grade 4 thrombocytopenia was seen in 32.2% with a bleeding event in two patients. Nonhematologic toxicities were mild. There were no drug-related toxic deaths., Conclusion: The relative high-dose of topotecan combined with carboplatin was feasible and produced modest activity in recurrent or persistent EOC. The RR and survival data appear promising for the initially platinum-sensitive cohort and thus this regimen may be considered for further development in this patient.