Potential efficacy of weekly low-dose administration of bevacizumab as a combination therapy for platinum-resistant ovarian carcinoma: a retrospective analysis.

BACKGROUND: Bevacizumab (Bev) plays the central role of the adjuvant therapy for patients with ovarian carcinoma. The aim of our study was to examine whether differences in the administration of Bev influence the prognosis of patients. METHODS: Patients with ovarian carcinoma who received treatment at two hospitals between 1999 and 2020 were identified. Patients treated with weekly low-dose administration of Bev (100 mg Bev on days 1 and 8 and 200 mg Bev on day 15, monthly) at one hospital (group A) and those with monthly high-dose administration of Bev (15 mg/kg of Bev on day 1, monthly) at another hospital (group B) were retrospectively compared. RESULTS: Among the total patients, 44 were assigned to group A and 33 were assigned to group B. More patients in group A had advanced disease (p = 0.03) and a lower dose of Bev at the first time during the first cycle administration (p < 0.01) than in group B. Progression-free survival (PFS) was better in group A than in group B (p < 0.01). Multivariate analysis revealed that group A was a better prognostic factor for PFS (hazard ratio 0.53, p = 0.03). Stable duration was longer in group A than in group B (p < 0.01). The incidences of adverse effects, including hematological toxicities such as neutropenia (p = 0.01) and nonhematological toxicities such as hypertension (p < 0.01), intestinal obstruction (p < 0.01), and thromboembolic events (p < 0.01), were lower in group A than in group B. CONCLUSIONS: Weekly low-dose administration of Bev might improve prognosis and decrease the frequency of adverse effects associated with this drug although the prospective study was needed to get corroboration.

Psoas muscle index at the fifth lumbar vertebra as a predictor of survival in epithelial ovarian cancers.

Almost a quarter of a century has passed since the term sarcopenia was defined. Sarcopenia is recognized as a poor prognostic factor in a variety of cancer types. In ovarian cancer, it remains controversial whether sarcopenia affects prognosis and how it should be evaluated. The present study aimed to evaluate the association between the volume of the psoas major muscle and survival in patients with epithelial ovarian cancer. Medical charts of patients with epithelial ovarian cancer who received first-line chemotherapy with paclitaxel and carboplatin at the National Defense Medical College Hospital (Tokorozawa, Japan) between April 2010 and January 2015 were retrospectively reviewed. The bilateral psoas major muscle areas at the fifth lumbar vertebra were measured using computed tomography images. The Institutional Review Board at National Defense Medical College Hospital (Tokorozawa, Japan) approved the study protocol. A total of 72 patients with epithelial ovarian cancer who received combination therapy with paclitaxel and carboplatin were identified and enrolled. The median psoas muscle index (PMI; psoas muscle major cross-sectional area divided by height squared) was 5.4 cm2/m2 (range, 3.3-10.0). Patients with higher PMI had significantly improved overall survival (OS) compared with those with lower PMI [log-rank test P=0.014; hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.21-6.06]. Multivariate analysis for OS revealed that lower PMI was an independent unfavorable prognostic factor (HR, 3.87; 95% CI, 1.37-12.1; P=0.0098). The volume of psoas major muscle mass could be a potential biomarker for prognosis in patients with epithelial ovarian cancer.

On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity.

Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au-S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm-1; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm-1, manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.

Pretreatment Neutrophil-to-Lymphocyte Ratio Was a Predictor of Lymph Node Metastasis in Endometrial Cancer Patients.

OBJECTIVE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported to be useful as markers for prognostic factors and metastasis in several cancers. The aim of this study was to identify the predictor of lymph node (LN) metastasis by pretreatment NLR and PLR in patients with endometrial cancer. METHODS: Medical charts of the patients with endometrial cancers that received primary surgery at our hospital between 2007 and 2013 were retrospectively analyzed. The cutoff value was calculated from the receiver operating characteristics (ROC) curve. Clinicopathological parameters including inflammatory markers were evaluated for LN metastasis using multiple logistic regression analysis. RESULTS: Among 197 patients enrolled in the study, LN metastasis was observed in 25 patients (13%). ROC curves demonstrated that the best cutoff value of NLR for predicting LN metastasis was 2.18 and that of PLR was 206. In univariate analysis, several pathological factors, NLR, and PLR were identified as predictors of LN metastasis. In multiple logistic regression analysis, lymphovascular invasion and NLR were found to be significantly correlated with LN metastasis (p = 0.002, 0.039). CONCLUSION: A higher pretreatment NLR was identified as a predictor of LN metastasis in endometrial cancers. Although further study is needed to confirm the results, NLR could be a candidate clinical marker for detection of LN metastasis.

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas.

OBJECTIVE: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. METHODS: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. RESULTS: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). CONCLUSION: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC.

A Pathological Study Using 2014 WHO Criteria Reveals Poor Prognosis of Grade 3 Ovarian Endometrioid Carcinomas.

BACKGROUND/AIM: The purpose of this study was to compare the clinical behavior of several grades of endometrioid carcinoma (EC) compared to high-grade serous carcinoma (HGSC), based on World Health Organization 2014 criteria. MATERIALS AND METHODS: Clinicopathological features were compared between all grades of EC and HGSC, and between HGSC and either grade 1/2 or grade 3 EC. RESULTS: Sixty-five patients with EC and 214 with HGSC were identified. Among patients with EC, 56 displayed 1/2 EC and nine had grade 3 EC. The progression-free (PFS) and overall (OS) survival of patients with grade 1/2 EC were better than of those of patients with HGSC; however, PFS and OS did not statistically differ between patients with grade 3 EC and those with HGSC. Grade 1/2 EC, but not grade 3, was a better prognostic factor compared with HGSC. CONCLUSION: A grading system for EC would be beneficial for the accurate prognosis of ovarian cancer.

JAK2/STAT3 pathway as a therapeutic target in ovarian cancers.

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.

Addition of bevacizumab to gemcitabine for platinum-resistant recurrent ovarian cancer: a retrospective analysis.

PURPOSE: To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev-Gem) to that of patients treated only with gemcitabine (Gem). METHODS: Between 2011 and 2017, we identified the Bev-Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev-Gem or Gem until disease progression or death. RESULTS: The Bev-Gem and Gem groups included 18 and 29 patients, respectively. More patients had advanced stage disease in the Bev-Gem group (p = 0.048); no other characteristics differed between the groups. The response rates [ratio of complete remission (CR) to partial remission (PR)] of Bev-Gem and Gem were 38.9 and 3.4%, respectively (p < 0.01). The clinical benefit rates [combined percentages of CR, PR, and stable disease] of the Bev-Gem and Gem groups were 88.9 and 41.4%, respectively (p = 0.04). PFS and OS of the Bev-Gem group were superior (p < 0.01, p = 0.03, respectively). Bev-Gem was the better prognostic factor of both PFS [hazard ratio (HR) 0.17, p < 0.01] and OS (HR 0.31, p = 0.01). The frequency of hematologic and non-hematologic adverse effects was similar in each group. CONCLUSION: Bev-Gem regimens improved PFS and OS for PROC. Furthermore, the adverse effects of Bev-Gem were tolerable. Thus, Bev-Gem could be a candidate treatment strategy for PROC.

Seromucinous component in endometrioid endometrial carcinoma as a histological predictor of prognosis.

OBJECTIVE: In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but "seromucinous carcinoma" was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients. METHODS: Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013. RESULTS: Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049). CONCLUSION: Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis.

Low Expression of CD44 Is an Independent Factor of Poor Prognosis in Ovarian Mucinous Carcinoma.

AIM: To determine whether CD44, which is associated with tumor growth and metastasis, is related to carcinogenesis and prognosis in ovarian mucinous carcinomas (MACs). MATERIALS AND METHODS: Tissue blocks from 71 patients with benign mucinous ovarian tumors were used in the study: 35 were from patients with borderline mucinous ovarian tumors, and 60 from patients with MACs. Immunochemical analysis was performed to evaluate the expression of CD44 and examine its association with tumorigenesis and survival. RESULTS: Compared to benign tumors, borderline tumors had high CD44 expression levels (p=0.047). Conversely, MACs had lower expression than borderline tumors (p=0.032). Progression-free and overall survival of patients with MAC with low CD44 expression were worse than those of patients with high expression (p=0.04 and p=0.02, respectively). CONCLUSION: Malignant transformation of mucinous tumors is associated with changes in CD44 expression, with low expression level being a prognostic factor in MAC.

Phenoxodiol Increases Cisplatin Sensitivity in Ovarian Clear Cancer Cells Through XIAP Down-regulation and Autophagy Inhibition.

BACKGROUND/AIM: To investigate whether XIAP down-regulation and autophagy inhibition sensitize ovarian clear cell cancer cells to cisplatin. MATERIALS AND METHODS: The ovarian clear cancer cell line KK was used for in vitro analysis. Hydroxychloroquine (HCQ) and phenoxodiol (PXD) or embelin were used as autophagy and XIAP inhibitors, respectively. Non-specific and XIAP-specific siRNAs were transfected using Lipofectamine. Cytotoxicity was assessed by MTT assays. Protein expression was confirmed by western blotting. RESULTS: In KK, down-regulation of XIAP using specific siRNAs together with HCQ treatment enhanced the anti-tumor effect of cisplatin. Although embelin sensitized KK to cisplatin through XIAP down-regulation, it induced autophagy. However, PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition. Expression of Atg7, Atg12, and Beclin 1 was decreased after PXD treatment. CONCLUSION: PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition and could be a new candidate for ovarian clear cell carcinoma treatment.

Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review.

PURPOSE: We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype. METHODS: Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m2 of CPT-11 on days 1, 8, and 15, and 50 mg/m2 of nedaplatin on day 1, q4 weeks. RESULTS: The median patient age was 63 years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status. CONCLUSIONS: The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma.

Role of endometriosis as a prognostic factor for post-progression survival in ovarian clear cell carcinoma.

The clinical significance of coexistence of endometriosis (EM) in ovarian clear cell carcinoma (CCC) has not yet been determined. The aim of the present study was to analyze the correlation of endometriosis with clinicopathological factors in CCC. The cases with CCC that received primary debulking surgery at the present hospital between 1990 and 2013 were identified. Retrospective analysis was conducted to evaluate the association between complications with EM and clinicopathological features in CCC. Of the 105 cases enrolled in the study, 45 cases were complicated with EM, and 60 cases did not have EM (non-EM). The patients with EM were diagnosed at a younger age (P=0.03), and at earlier stages (P<0.01) compared with non-EM cases. Although there was no significant difference of progression-free survival (P=0.36), complications with EM were identified as an independent prognostic factor for overall survival (OS; P<0.01) by multivariate analysis. A total of 48 patients (45.7%) developed recurrence: 18 patients in EM-group and 30 patients in non-EM group. There were no significant differences of clinicopathological factors in the treatment at recurrence between both groups. Recurrent cases in EM had significantly worse post-progression survival (PPS) compared with recurrent non-EM group (P<0.01). Multivariate analysis for PPS demonstrated that complications with EM (P<0.01) were identified as a worse prognostic factor. In CCC, the complication with EM was identified as a significant worse prognostic factor for PPS in recurrent cases. Additionally, EM was significantly associated with OS in all cases with CCC. Novel treatment strategies are therefore necessary for recurrent CCC, particularly for cases exhibiting EM.

Ovarian serous carcinomas acquire cisplatin resistance and increased invasion through downregulation of the high-temperature-required protein A2 (HtrA2), following repeated treatment with cisplatin.

High-temperature-required protein A2 (HtrA2) is one of the serine proteases related to apoptosis. HtrA2 protein expression has been associated with cisplatin resistance and poor prognosis in ovarian serous adenocarcinoma (SAC). The aim of this study was to understand the influence of HtrA2 on repeated treatment with cisplatin. The change in HtrA2 expression in 31 ovarian cancers was investigated by immunohistochemical analysis, before and after cisplatin-based chemotherapy, and the association between HtrA2 expression after chemotherapy and prognosis was analyzed. The association between the change in HtrA2 and proteins associated with LATS1 in ovarian serous cancer cell lines after repeated treatment with cisplatin was evaluated in vitro. In immunohistochemical analysis, repeated cisplatin treatment induced downregulation of HtrA2 protein expression, before and after cisplatin-based chemotherapy in SAC. Progression-free survival and overall survival of SAC with low expression of HtrA2 were worse than those with high expression. In vitro analysis using cisplatin-sensitive ovarian cancer cell lines, KF28, and cisplatin-resistant cancer cell lines, KFr13, obtained from KF28 by repeated cisplatin treatment, showed that HtrA2 protein expression was lower in KFr13 than in KF28. Furthermore, KFr13 had a higher invasive capacity than KF28. Next, downregulation of HtrA2 transfected with an HtrA2-specific siRNA in KF28 had not only cisplatin resistance, but also more invasive capacity than those with non-specific siRNA. Repeated treatment with cisplatin downregulated the HtrA2 protein, which led to cisplatin resistance and increased invasive capacity. Thus, HtrA2 might be a biomarker of response to cisplatin treatment and prognosis, after cisplatin-based chemotherapy.

Factors favouring long-term survival following recurrence in ovarian cancer.

The aim of the present study was to identify clinicopathological factors in long-term survivors following ovarian cancer recurrence. The patients who achieved longer survival after recurrence (n=18) and those who succumbed to the disease earlier (n=47) were identified and analyzed. There were no significant differences in age, performance status, stage distribution or histology between the two groups. Additionally, no significant difference was observed in progression-free survival after primary therapy. Multivariate analyses revealed that the predictive factors for long-term survival were i) secondary debulking surgery (OR=13.3; 95% CI: 1.39-226.7), ii) favourable response rate of second-line chemotherapy (OR=46.5; 95% CI: 1.84-313-4), and iii) ≥3 regimens after first recurrence (OR=9.01; 95% CI: 1.28-117.7). This study revealed that prolonged post-progression survival was associated with post-recurrence treatment. Therefore, appropriate selection of secondary debulking surgery and better chemotherapeutic response may lead to prolonged post-progression survival in recurrent ovarian cancer patients.

Combination of irinotecan and platinum for platinum-resistant or refractory recurrent ovarian cancers: A preliminary case series.

Non-platinum single agents are usually used for patients with platinum-resistant recurrent ovarian cancers (ROC). However, the efficacy of these drugs is limited. The aim of the present study was to evaluate the efficacy and adverse events (AE) of combination therapy with irinotecan and platinum (CPT-Pt) for ROC. A total of 28 platinum-resistant or refractory patients with ROC treated with CPT-Pt at the National Defense Medical College Hospital institution between 2002 and 2012 were identified. All patients received taxane and carboplatin (TC) as a first-line treatment and relapsed within 6 months after completion of TC, or progressed during TC therapy. The median age was 59 years (range, 16-78), and median number of CPT-Pt therapy cycles was 5.5 (range, 2-16). The overall response rate was 14%, with a complete response (CR) in 2 patients and partial response (PR) in 2 patients. Stable disease (SD) for >3 months was observed in 15 patients (54%), resulting in a clinical benefit rate (CBR = CR + PR + SD) of 68%. The median progression-free survival and overall survival were 8 and 15 months, respectively. Fifteen cases (68%) developed grade 3/4 hematological AE and 3 cases (11%) developed non-hematological grade 3/4 AE, which were resolved by conservative management or dose reduction. Platinum re-treatment with irinotecan for platinum refractory or resistant ROC may be a candidate in such clinical settings.

Psoas muscle volume as a predictor of peripheral neurotoxicity induced by primary chemotherapy in ovarian cancers.

PURPOSE: Low skeletal muscle mass (sarcopenia) has been reported to have an influence on survival and toxicities of chemotherapy in several solid tumors. The impact of sarcopenia on the treatment of ovarian cancers has not been determined. The present study aimed to evaluate correlation between sarcopenia and toxicities of chemotherapy in ovarian cancers. METHODS: Medical charts of the ovarian cancer patients that received chemotherapy with paclitaxel and carboplatin at our hospital between 2010 and 2015 were retrospectively reviewed. Muscle areas of bilateral psoas major muscles at the fifth lumbar vertebra were measured using images obtained by computed tomography. The volume of muscle and clinicopathological factors were evaluated for toxicities of chemotherapy. The protocol of the present study was approved by the institutional review board of our institution. RESULTS: A total of 76 patients with ovarian cancers were identified, and enrolled in the present study. Median psoas index (PI, the psoas muscle major cross-sectional area divided by the height squared) was 583 mm2/m2 (range 326-999). The patients with low PI developed peripheral neuropathy more frequently compared with those with high PI (32 vs. 11%; P = 0.047). PI value was not associated with other toxicities such as neutropenia and thrombocytopenia. PI value was associated with grade 2 or higher peripheral neuropathy in univariate analysis (OR = 3.92; 95% CI 1.21-15.32; P = 0.02) and multivariate analysis (OR = 3.93; 95% CI 1.17-15.87; P = 0.03). CONCLUSIONS: PI value was significantly associated with peripheral neuropathy induced by combination therapy with paclitaxel and carboplatin in ovarian cancer patients. Although further studies are needed to confirm the results, the volume of skeletal muscle mass could be a potential biomarker to predict toxicities in ovarian cancer patients.

Is there any predictor for hypersensitivity reactions in gynecologic cancer patients treated with paclitaxel-based therapy?

PURPOSE: Recently, generic drugs of paclitaxel have been commonly used mainly by economic reasons; however, predictive factors for toxicities are not fully determined. Hypersensitivity reaction (HSR) is one of the most important adverse events in the paclitaxel-based therapy, and sometimes leads to lethal condition. The aim of the study was to identify predictors for HSR in patients treated with paclitaxel-based regimens. METHODS: All the patients treated with chemotherapy including paclitaxel at our hospital between 1998 and 2013 were retrospectively evaluated. Clinicopathological factors of the patients that developed HSR and those without HSR were compared, and predictive factors for HSR were identified. RESULTS: Among 414 patients enrolled in the study, 26 patients (6.3%) developed HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1) were identified as predictive factors for HSR. There was no significant difference in the incidence of HSR between original paclitaxel and generic drug. The incidence of HSR was higher as the number of these predictors was accumulated. CONCLUSIONS: Three factors were identified as predictive factors for HSR: younger age, a history of allergy, and short-course premedication. Accumulation of these factors increased the incidence of HSR; however, the use of generic drug was not associated HSR in gynecologic cancer patients.