bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of all-intraperitoneal carboplatin and paclitaxel regimen shows good tolerability and efficacy for advanced ovarian cancer
Authors: Krasner C. N. , Seiden M. V. , Fuller A. F. , Supko J. G. , Roche M. , Kendall D. L. , Lee J. , Berkowitz R. , Berlin S. , Matulonis U. A. ,   Dana-Farber/Harvard Cancer Center Gynecologic Oncology Research Group
Published: March 2020

5521 Background: A phase III trial (GOG 172) demonstrated improved survival for patients (pts) with optimally-debulked ovarian cancer treated with intraperitoneal (IP) cisplatin and paclitaxel, as compared with standard IV dosing. Studies to further enhance efficacy and minimize toxicity of IP platinum/taxane regimens are needed. We present the clinical results of a novel IP regimen in follow-up to the pharmacokinetics (pk) results presented last year. Methods: Carboplatin at an AUC 6 on day 1 and paclitaxel 60 mg/m2 on days 1, 8, 15 was given, IV in cycle 1 and IP in the 5 subsequent 21-day cycles. The initial IV cycle was designed to allow for intra-patient IV vs. IP pk comparison. Pts completing 6 cycles with clinical complete response (CCR) underwent second-look operation (SLO). Results: Accrual is complete with 40 evaluable pts, 8 pts remain on trial. Pts came off study for: port-related complications (7), allergy (2), heme tox (2), vaginal leak (2), and infection (4). Toxicity was mild, with grade 3 or 4 toxicity consisting of neutropenia: 10 (25%), plts: 2 (5%), vomiting: 2 (5%), fatigue: 2 (5%) and anemia: 1 (2.5%). There was no grade 3 or 4 peripheral neuropathy or alopecia. Completion rate was good with 82% of pts completing = 4 cycles, as compared with 52% in GOG 172. All pts completing chemotherapy were judged to be in CCR; there was no progressive disease on trial. Of the pts undergoing SLO, 14 pts were negative, 4 pts were positive, for complete pathological response rate of 78%. Conclusions: Pts were able to complete more cycles of therapy on this regimen as compared with GOG 172. The incidence of gastrointestinal, metabolic, and neurotoxicity is very low. Preliminary SLO rate compares favorably to the 57% seen in GOG 172. Previously reported pk results as well as tolerability and efficacy are encouraging and suggest this regimen should be studied in a larger population. Final toxicity and response data will be available. No significant financial relationships to disclose.
A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel (Tax), IP cisplatin (Cis), and IV bevacizumab (Bev) as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer
Authors: Konner J. A. , Fallon K. , Pezzuli S. , Iasonos A. , Sabbatini P. , Hensley M. , Chiang A. , Tew W. , Spriggs D. , Aghajanian C. 
Published: March 2020

5523 Background: IP Cis plus IV/IP Tax is a standard therapy for optimally debulked ovarian cancer. Bev is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor (VEGF). Activity of Bev against recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy to assess safety and tolerability. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS = 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev (starting cycle 2): Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1. Extended treatment with Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. The study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by the proportion of patients who complete the prescribed 6 cycles of cytotoxic chemotherapy without discontinuation and without dose-limiting non-hematologic and non-electrolyte toxicity. A stopping rule will be applied if excessive toxicity is encountered. Results: To date, 8 women have been treated on the study. Median age: 53 (48–59). All 31 planned doses of chemotherapy have been administered in full. One dose of IP Tax was delayed for 2 days due to abdominal pain. One patient had her first dose of Bev delayed for 1 cycle due to surgical wound infection. There have been no toxicities > grade 3. Grade 1/2 toxicities include: fatigue (87.5%); nausea (50%); and hypomagnesemia (37.5%). Grade 3 toxicities per patient: fatigue (12.5%); hyponatremia (25%); hypokalemia (25%); hypertension (12.5%); abdominal pain (12.5%); and neutropenia (12.5%). Of the 5 patients with pretreatment CA125 >35 Units/mL, 4 normalized their value after 1 cycle of chemotherapy and 1 patient normalized after 2 cycles. Conclusions: Preliminary experience suggests that the combination of IV Bev with IP Cis plus IV/IP Tax may be well tolerated. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.
Impact of NCI Clinical Announcement upon use of chemoradiation for women with cervical cancer
Authors: Trimble E. L. , Gius D. , Harlan L. C. 
Published: March 2020

5537 Background: On the basis of 5 NCI-sponsored randomized phase III trials, in 1999 the NCI issued a Clinical Announcement recommending that women with cervical cancer who require radiation also receive concomitant platinum-based chemotherapy. We undertook a population-based cohort study to determine whether the 1999 NCI Clinical Announcement was associated with changes in clinical practice in the United States. Methods: Through the NCI’s SEER program, we identified 973 women with invasive cervical cancer diagnosed in 1997, 773 diagnosed in 2000, and 1370 diagnosed in 2001. Hospital records were re-abstracted and treated physicians were contacted to verify initial therapy provided to each patient. Results: In multivariate analysis, we found a significant increase in the use of chemoradiation between 1997 and 2001/2001 among women with cervical cancer of all stages for which radiation would be appropriate. (see table ). Compared to women with well-differentiated tumors, women with moderately or poorly differentiated tumors were more likely to receive chemoradiation. Women aged 75 years or older were significantly less likely to receive chemoradiation than younger women. We saw no impact of race/ ethnicity or insurance status upon receipt of chemoradiation. Conclusions: Publication of the results from these 5 sutdies, extensive professional educational efforts, and the NCI’s Clinical Announcement were associated with widespread adoption of chemotherapy in the treatment of cervical cancer in the United States. [Table: see text] No significant financial relationships to disclose.
Population-based study of the incidence, mortality and prognostic factors of small cell carcinoma of the cervix: Analysis of the Surveillance, Epidemiology and End Results database
Authors: Chen J. , MacDonald O. K. , Gaffney D. K. 
Published: March 2020

5546 Background: Small cell carcinoma (SmC) is a rare histology of the cervix uteri that is generally associated with a poor prognosis. This is a population-based study of SmC using the Surveillance, Epidemiology and End Results (SEER). Methods: From 1977 to 2003, 290 women with SmC of the cervix uteri were identified. In addition, 27,527 patients with squamous cell carcinoma (SC) and 5231 with adenocarcinoma (AC) of the cervix were identified for comparison. The annual incidence of each histology was determined and examined for trend. The patient and disease characteristics at diagnosis were examined for each histology, and prognostic factors were evaluated for SmC. Mortality rates of SmC and other histologies were compared via log-rank tests. Results: Mean annual incidence of SmC was 0.03 per 100,000 women compared to 3.5 and 0.62 for SC and AC. A significant change in incidence was identified for SC and AC (p<0.05), but not for SmC (p=0.595). Patients with SmC were more likely to be treated with radiotherapy and to present with more advanced stage, lymph node involvement and distant metastasis than SC and AC (p<0.05). Survival rates for SmC at 2 and 5 years were 46.8% and 35.7%, which were worse compared to SC (HR 0.45; 95% CI: 0.36–0.57) and AC (HR 0.31; 95% CI: 0.25–0.39). The difference in survival is predominantly in patients with early stage, localized disease, and those treated with surgery ( Table ). Multivariate analysis of SmC, race, FIGO stage, age and hysterectomy alone significantly impacted prognosis (p<0.05), while year of diagnosis, lymph node involvement, tumor size, marital status and other treatment modality did not. Conclusions: SmC is an uncommon histologic variant of cervix cancer associated with a worse prognosis compared to SC and AC with a predilection for metastasis at diagnosis. FIGO stage, age and race are prognostic factors for survival. [Table: see text] No significant financial relationships to disclose.
Induction of VEGF secretion in ovarian cancer by PDGF BB
Authors: Matei D. , Kelich S. , Cao L. , Menning N. , Emerson R. , Emerson R. , Rao J. , Sledge G. 
Published: March 2020

5557 Background: We identified the PDGFR as a potential target in epithelial ovarian carcinoma (EOC). This led us to test whether inhibition of the receptor affects ovarian cancer cell proliferation and survival and regulates other processes critical to tumor growth and metastasis. We postulated that the PDGF-PDGFR axis regulates VEGF secretion in EOC. Methods: VEGF secretion in ovarian tumors, cancer cells, serum and ascites was measured by IHC, Western Blot and ELISA. The HOG Gyn03–62 protocol was a phase II protocol for patients with recurrent platinum resistant EOC. Patients were treated with imatinib and docetaxel. Serum and tumor samples from patients enrolled on this protocol were analyzed for VEGF. Results: VEGF expression was quantified by IHC in ovarian tumors. Of 21 PDGFR expressing ovarian tumors, seven specimens immunostained strongly for VEGF and six tumors demonstrated 2+ VEGF reactive extracellular (secreted) material. PDGF and VEGF secretion was measured in 17 specimens of malignant EOC ascites. The levels of PDGF BB and VEGF were strongly correlated (Pearson coefficient =0.728, p-value=0.001), suggesting that the two pathways interconnect. There was no correlation between PDGF AA and VEGF levels. VEGF levels were measured in 13 paired serum samples from patients enrolled in the clinical protocol HOG: Gyn03–62, before and after treatment. VEGF serum levels were stabilized or decreased in 9 of 13 EOC patients treated with imatinib. In conditioned media from primary cells, VEGF secretion was four fold higher for tumor derived cells than for cells derived from the normal ovarian epithelium. PDGF increased ten-fold VEGF secretion in PDGFR expressing immortalized ovarian cells (C272/hTert/E7 and C889/hTert), while imatinib reduced VEGF production to basal state. The effects of imatinib were mediated via inhibition of Akt and MAPK pathways, by stabilization of HIF1 alpha. In ovarian cancer cells overexpressing consitutively active Akt, imatinib inhibited only partially the secretion of VEGF compared to control cells, suggesting that the PI3K/Akt pathway is significantly implicated in PDGF-stimulated VEGF secretion. Conclusions: These results suggest that by blocking the PDGFR, imatinib inhibits VEGF production. This affects the tumor microenvironment favoring ovarian tumor growth and metastasis. No significant financial relationships to disclose.
Recurrence in ovarian carcinoma stage I A/B grade 1 and 2 with and without chemotherapy
Authors: Simpkins F. , Abu Shahim F. , Bakkum-Gamez J. N. , Jones M. B. , Rocconi R. P. , Mathews K. S. , Moore K. N. , Fong D. N. , Rose P. G. 
Published: March 2020

5565 Background: The goal of this study was to determine the recurrence rates (R) of patients with grade 1 and 2 stage 1A and IB ovarian tumors treated with and without chemotherapy. Methods: We conducted a five-center retrospective study of patients with Stage 1A/B grade 1 and 2 ovarian carcinoma. All women underwent comprehensive staging including a minimum of unilateral salpingo-ophorectomy, unilateral pelvic and para-aortic lymphadenectomy, and omentectomy. Clear cell histologies were classified as grade 3 and excluded. The minimum cancer-free survivor follow-up was 3 years. Results: We identified 82 patients with Stage 1A/B grade 1 and 2 who met criteria for the study. The median age was 58 yrs (range 29 to 83) and the median follow-up was 5.3 yrs (range 3 to 11 yrs). The majority were of endometrioid histology (51), followed by mucinous (19), papillary serous (11), and mixed (1). Recurrences were of endometrioid (4), mucinous (1), or papillary serous (1) histology. For Stage 1A, overall recurrence rate was 9% (6/67). The overall recurrence rates for Stage 1A, grade1 tumors was 6% and among grade 2 tumors 12% (p=0.40). Among Stage 1A patients not treated with chemotherapy, there was a 7% (2/29) and 9.5% (2/21) recurrence rate for grade 1 and grade 2 tumors, respectively. For the grade 1 tumors, both patients are alive with disease at 3 and 5 yrs. For the grade 2 tumors, one is alive without evidence of disease at 7 yrs and the other died from disease at 4 yrs. Time to recurrence (TTR) was 2.3 yrs for grade 1 tumors and 2.6 yrs for grade 2 tumors. For Stage 1A patients treated with a platinum chemotherapy regimen, there were no recurrences (0/5) for grade 1 tumors and a 16% (2/12) recurrence rate for grade 2 tumors. Of the recurrences, one patient died from disease at 1.4 yrs and the other is alive with stable disease at 6 yrs. Time to recurrence was 2.85 yrs for grade 2 tumors. For grade 1 or 2, Stage 1A tumors, recurrence rates and time to recurrence were not effected by chemotherapy administration (R, p=0.55 and p=0.54, respectively; TTR, grade 2, p=0.85). No recurrences were observed in the 15 patients with Stage IB, grade 1 and 2 tumors. Conclusions: In comprehensively staged patients with Stage 1A/B, grade 1 and 2, low recurrence rates suggest adjuvant chemotherapy may not be indicated. No significant financial relationships to disclose.
Neoadjuvant chemotherapy for low-grade serous carcinoma of the ovary
Authors: Schmeler K. M. , Sun C. C. , Bodurka D. C. , Deavers M. T. , Coleman R. L. , Ramirez P. T. , Gershenson D. M. 
Published: March 2020

5571 Background: Neoadjuvant chemotherapy (NACT) has been associated with significant tumor reduction prior to interval debulking surgery, enabling optimal cytoreduction in up to 50% of patients with high-grade ovarian carcinomas deemed initially unresectable. Since low-grade serous carcinoma (LGSC) appears to be relatively less chemosensitive, we sought to evaluate the outcomes of women with ovarian LGSC treated with platinum-based NACT. Methods: Using institutional databases, we identified 18 women with low-grade serous carcinomas of the ovary who were treated with neoadjuvant platinum-based chemotherapy between 1978 and 2003. Patient demographic and clinical variables were abstracted from the medical records. Progression-free survival (PFS) and overall survival (OS) were estimated using the method of Kaplan-Meier. Results: The median age at diagnosis was 44 years (range, 21 to 81 years). NACT was given for extensive or non-resectable disease in 16 patients (89%) and for unknown reasons in 2 patients (11%). Ten patients (42%) underwent exploratory laparotomy with biopsy only prior to beginning chemotherapy. A median of 6 cycles of chemotherapy was given (range, 2 to 16) and included the following regimens: platinum/taxane (n=12 patients); platinum/cyclophosphamide (n=3 patients); and platinum/leuprolide acetate (n=3 patients). Of the 13 patients who had CA-125 levels available, 8 (62%) had a ≥50% reduction between pre- and post-NACT levels. However, response, determined by radiographic survey at completion of NACT, demonstrated one patient (6%) with a complete response, no patients (0%) with a partial response, and 16 patients (89%) with stable disease. One patient (6%) was not evaluable. Fifteen patients (83%) underwent interval cytoreductive surgery, which was optimal in 8 cases (53%), suboptimal in 4 cases (27%) and unknown in 3 cases (20%). Median PFS and OS for all patients were 18.6 and 56.1 months, respectively. Conclusions: A low response rate to platinum-based NACT was observed among women with LGSC of the ovary. These findings suggest that LGSC is not as responsive to conventional chemotherapy as high-grade serous carcinoma. Prospective clinical trials, focusing specifically on LGSC, are needed to make meaningful advances for this group of patients. No significant financial relationships to disclose.
Prediction of survival in patients with epithelial ovarian cancer based on the timing and rate of normalization of CA125 levels during primary chemotherapy
Authors: Matthews K. S. , Rocconi R. P. , Kemper M. , Hoskins K. E. , Huh W. K. , Wang W. , Straughn J. M. 
Published: March 2020

5585 Objective: CA125 is the tumor marker used to evaluate response to chemotherapy in patients with epithelial ovarian cancer (EOC). The aim of this study was to determine if the timing of normalization or percent decrease in CA125 levels during primary chemotherapy could predict survival. Methods: Patients treated at our institution for EOC with primary taxane/platinum-based chemotherapy for 6 cycles between 1996 and 2005 were eligible. Patient demographics, chemotherapy administration, CA125 levels, and survival outcomes were abstracted. Progression-free- survival (PFS), overall survival (OS), and platinum sensitivity (> 6 months from chemotherapy completion) were compared to CA125 levels during primary therapy. Baseline levels, change over time, and timing of CA125 normalization were calculated. Analyses were performed using Kaplan-Meier method and compared using the log-rank test, Chi-square test and Fischer’s exact test. Results: 269 patients with EOC were identified. When stratified by which cycle of chemotherapy achieved normalization, PFS ranged from 25 months at 1st cycle to 4 months at 6th cycle (p< 0.001). OS showed a similar benefit from 74 months at 1st cycle to 22 months at 6th cycle (p<0.001). Platinum sensitivity improved from 23% (normal CA125 after 6th cycle) to 72% (normal CA125 after 1st cycle) (p=0.003). Patients with normalization after the 3rd cycle or sooner compared to patients with normalization after the 4th cycle demonstrated improved PFS (19 vs. 6 months; p<0.001), OS (48 vs. 27 months; p=0.001) and platinum sensitivity (78 vs. 22%; p<0.001). Linear regression models of the slope of the decline of CA125 levels correlated with PFS (p=0.03); however, the models failed to predict an OS advantage. Conclusion: Earlier normalization of CA125 levels during primary chemotherapy for EOC predicts improvement in platinum sensitivity, PFS, and OS. This data provides prognostic information that may influence future decisions regarding chemotherapy. No significant financial relationships to disclose.
Treatment and prognosis of epithelial ovarian cancer in Iran
Authors: Khodabakhshi R. , Yahyazadeh Jabbari S. , Gohari M. , Sadrolhefazi B. , Mosavizadeh A. , Shahidi J. , Ameri A. , Madani H. , Sharifi B. , Bahor F. 
Published: March 2020

5586 Background: Ovarian cancer is the most lethal gynecologic malignancy in the US, with 14,500 women dying of this disease annually. The aims of this study are to describe brief epidemiologic variations, response rate for usual chemotherapy regimen and progression free survival analysis in Iranian patients. Patients and Methods: 98 women with confirmed ovarian cancer who have been undergone surgery followed by chemotherapy at three hospitals in Tehran (Iran) between 1997 and 2003 were enrolled in this retrospective study. FIGO staging system has been applied. We have collected data regarding age, pathologic variations, surgical procedure (complete, partial, biopsy), chemotherapy, response rate, and time to progression of disease. Results: From a total of 98 patients, there were 80 (81.6%) epithelial, 12 (12.2%) germ cell, 5 (5.1%) granulosa cell tumors and one case of lymphoma. Response rate have been evaluated for 60 patients with epithelial cancer. Overall mean age was 46.7 and average age for epithelial tumors and non-epithelial tumors were 49.6 and 34.3 respectively. Complete surgical procedure with staging and optimal residue had been performed for 18 patients. Stage III was the most common stage (46.1%). In 78.3% of patients complete or partial response were seen, while 21.7% of patients showed stable or progressive disease. The most important prognostic factors were stage, and extent of surgical procedure. Median progression-free survival was 24.2 months. Conclusion: Overall average-age of our patients is lower than expected. Besides, a large proportion of the patients are referred in advanced stages. Although, higher response rate has been produced by taxane-based regimen in comparison of traditional chemotherapy; but it was not statistically significant. Retrospective evaluation, low number of the patients, non-uniform usage of chemotherapy regimen could influence our results. No significant financial relationships to disclose.
A phase II multicenter trial of paclitaxel and carboplatin in women with advanced or recurrent malignant mixed müllerian tumors (MMMT) of the uterus
Authors: Ramondetta L. M. , Lacour R. A. , Euscher E. D. , Iyer R. B. , Atkinson E. N. , Gano J. B. , Milam M. R. , Ramirez P. T. , Levenback C. F. , Burke T. W. 
Published: March 2020

5589 Background: Systemic therapy for advanced malignant mixed müllerian tumor of the uterus (MMMT) after surgery has been disappointing. Currently, the most common treatment regimen is ifosfamide and platinum. Moderate success has been documented using paclitaxel in MMMT of the ovary. The purpose of this study is to evaluate carboplatin and paclitaxel in patients with advanced (IIIb-IVb) and recurrent MMMT of the uterus. Methods: A single arm, prospective, non-randomized phase II trial opened in October 2001. The planned sample size is 37 evaluable patients, with time to progression and response rate as the primary endpoints. Patients receive carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 21 days. Patients treated adjuvantly receive a total of 6 cycles or until progression or toxicity. Patients with disease present at study entry are treated until progression or toxicity. Results: To date, 18 patients have been enrolled. Seven patients received adjuvant treatment and 11 patients had documented disease at study entry. In the adjuvant group, the median progression-free interval was 15.8 months and median overall survival from treatment initiation was 20.2 months. Four of these 7 patients (57%) continue to be followed with a median follow-up of 19.2 months. In the patients with documented disease, the median progression- free interval was 7.8 months and the median overall survival from treatment initiation was 12.4 months. In this group, there were 3 complete and 4 partial responses (63.6% response rate). Over 45% of patients with disease at study entry are alive with a median follow-up of 14.0 months. Four patients experienced grade 4 granulocytopenia. Only two (11%) had treatment-limiting toxicity, one with grade 3 neuropathy and one with grade 3 fatigue. Conclusions: Carboplatin and paclitaxel appear to have improved tolerability and response rate (63.6%) compared to previous reports of ifosfamide and cisplatin (33% RR) in treating MMMT of the uterus. This regimen seems extremely promising and we are awaiting the final results of this trial. No significant financial relationships to disclose.