- Email: [email protected]
Hyperthermic intraperitoneal chemotherapy with carboplatin for recurrent epithelial ovarian cancer: A pilot study
Abstracts / Gynecologic Oncology 130 (2013) e1–e169
Objective: We investigated the significance of dose intensity on survival compared with treatment delay in adjuvant chemotherapy. Methods: Medical records of 429 patients diagnosed with epithelial ovarian cancer (EOC) between 2005 and 2011 were reviewed retrospectively. Relative dose intensity (RDI) was calculated with the ratio of delivered dose intensity to standard dose intensity. Multivariate analysis was performed to identify a prognostic significance of treatment delay and dose reduction to tumor recurrence. Results: Ninety-nine EOC patients received 6 cycles of postoperative adjuvant chemotherapy with paclitaxel and carboplatin. Mean values of RDI, treatment time intensity, and injected dose intensity were 93% (range, 70%-110%), 106% (range, 97%-127%), and 98% (range, 87%-110%), respectively. Most common causes of decreased RDI were neutropenia and thrombocytopenia. Median progression-free survival (PFS) of patients who received chemotherapy with b90% of dose intensity was 11 months compared with 21 months for patients who received N90% of dose intensity. In contrast with treatment time delay, dose intensity was an independent prognostic factor for tumor recurrence with multivariate analysis (P = 0.030, 95% CI 1.307208.203). Conclusions: Dose reductions and treatment delays are the main ways to achieve an RDI for patients with chemotherapy-induced toxicity. Maintaining more than 90% of dose intensity is a significant factor in prolonging PFS. doi:10.1016/j.ygyno.2013.04.353
295 Successful oxaliplatin salvage for recurrent ovarian cancer after carboplatin/cisplatin allergy S. Taylor, T. Beck, T. Krivak, K. Zorn, J. Kelley, R. Edwards. MageeWomen’s Hospital of UPMC, Pittsburgh, PA. Objective: Hypersensitivity reactions preclude platinum re-challenge for up to 44% of patients receiving second-line and higher carboplatin/ cisplatin salvage therapy. Our center has used oxaliplatin challenge for platinum hypersensitivity since 2006. The objective of this study was to evaluate our patient experience in recurrent or progressive ovarian or fallopian tube cancer with oxaliplatin salvage. Methods: This is a single-institution, retrospective chart review of all patients from 1995 to 2012 receiving oxaliplatin for treatment of recurrent or progressive ovarian or fallopian tube carcinoma. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval, prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. All patients who received oxaliplatin for 1 or more cycles were included. A response to therapy was determined after 2 or more cycles. Results: We identified 44 patients who received oxaliplatin as treatment for epithelial ovarian or fallopian tube carcinoma. All patients had prior carboplatin therapy and 38.6% (17/44) had prior cisplatin therapy. Platinum hypersensitivity reactions were seen in 52.3% (23/44). Patients received a median of 2 prior platinum-containing chemotherapy regimens and a median of 5 chemotherapy lines before oxaliplatin exposure. No grade 3 or grade 4 toxicities were noted. No patients had treatment delays for pancytopenia. Nausea and dysesthesias were controlled medically and were not dose-limiting. No platinum-associated toxicities, such as nephropathy or neuropathy, progressed on oxaliplatin therapy or were dose-limiting. Disease response was seen in 56.8% of patients, with a median reduction in CA-125 to 55.3% of the starting level. In patients who responded to therapy, the median nadir of CA-125 was 19.1% of the starting level. Of those patients who responded to oxaliplatin therapy, 42.3% had a prior platinum hypersensitivity reaction and were not candidates for other platinum-containing
e123
regimens. Patients were followed for a median of 15.5 months (range, 1-46 months) after initiation of oxaliplatin therapy. Conclusions: In our institution’s experience, oxaliplatin is well tolerated and should be considered for platinum challenge desensitization after carboplatin/cisplatin hypersensitivity with a reasonable chance of response. doi:10.1016/j.ygyno.2013.04.354
296 Platinum dosing for epithelial ovarian cancer: Is it appropriate to use actual body weight? J. Martin, M. Shah, B. Erickson, L. Daily, D. Pasko, C. Walters, J. Fauci, K. Bevis. University of Alabama at Birmingham, Birmingham, AL. Objective: Rates of obesity in the United States continue to rise. Historically, obese patients with ovarian cancer have received adjusted-dose (AD) chemotherapy due to concerns for increased toxicity without corresponding benefit. However, there is evidence that chemotherapy pharmacokinetics in obese patients differ from those in normal-weight patients, and dose restriction (DR) may lead to poorer outcomes. Recently published guidelines by the American Society for Clinical Oncology recommend using the patient’s actual, as opposed to ideal, body weight. We sought to determine the rate of DR in our epithelial ovarian cancer (EOC) patient population and if that influenced outcomes. Methods: We conducted a retrospective review of EOC patients diagnosed between 2004 and 2009 at a single institution. Demographic data, tumor characteristics, and primary treatment details, including chemotherapy dosing, were abstracted. Only women who received 4 or more cycles of intravenous platinum/taxane regimens were included. Patients were considered DR if their total platinum dose was b90% of that predicted based on actual body weight. Student’s T-test and chisquare analysis were used to compare variables as appropriate. Results: Of 211 patients who met inclusion criteria, 98 (46%) were platinum dose-restricted. On average, DR women received 25% less platinum than their actual body weight dose would have predicted. The mean body mass index (BMI) of DR women was 32.3 compared to 23.9 among appropriately dosed (AD) women (P b 0.01). The 2 groups were the same in regard to race, stage, debulking status, and histology, although DR women were significantly younger (60.0 vs. 65.5 years, P b 0.01). Progression-free survival (PFS) and overall survival (OS) were not different (PFS 24.1 vs. 22.66 months, P = 0.59; OS 34.1 vs. 35.4 months, P = 0.61). AD women with a BMI N30 had a significantly shorter OS compared to DR women with a BMI N30 (26.8 vs. 37.3 months, P = 0.03). These groups did not differ in terms of debulking status, stage, or histology. However, the AD/BMI N30 group were significantly older than the AD/BMI N30 group (70.6 vs. 59.7 years, P = 0.02). Conclusions: Obese patients with EOC commonly receive substantially lower doses of platinum when treated based on ideal body weight, but this does not appear to affect PFS or OS. However, older women with a BMI N30 have a significantly worse survival when dosed on actual body weight. This issue warrants further investigation. doi:10.1016/j.ygyno.2013.04.355
297 Hyperthermic intraperitoneal chemotherapy with carboplatin for recurrent epithelial ovarian cancer: A pilot study T. Sueblinvong1, P. Argenta1, M. Geller1, L. Downs1, A. Jonson1, L. Carson1, J. Ivy1, P. Judson Lancaster2. 1University of Minnesota, Minneapolis, MN, 2Moffit Cancer Center, Tampa, FL.
e124
Abstracts / Gynecologic Oncology 130 (2013) e1–e169
Objective: To evaluate the feasibility and tolerability of hyperthermic intraperitoneal carboplatin (HIPC) following secondary cytoreduction for recurrent, platinum-sensitive ovarian cancer. Methods: A single-institution prospective pilot study. Ten patients underwent secondary cytoreductive surgery followed by HIPC with carboplatin at 1,000 mg/m2. Consolidation (6 cycles) was with standard platinum-based regimens. Adverse events (AE) were monitoring according to CTCAE v4.0 guidelines. Quality of life was measured before surgery, within 1 week of HIPC-carboplatin, and at the conclusion of therapy using FACT-O tool. Results: Twelve patients were enrolled of which 2 were excluded (1 each for extra-abdominal disease identified before surgery and suboptimal cytoreduction). All 10 remaining patients received prescribed HIPC. There were no intraoperative complications or AEs attributable to HIPC therapy. Grade 1/2 nausea was the most common postoperative toxicity (6/10 patients), but this was managed with oral and/or antiemetics. Two patients had grade 4 postoperative neutropenia and thrombocytopenia, but only 1 experienced transient treatment delay. The median hospital stay was 5.5 days. A total of 69/70 (98%) planned chemotherapy doses were ultimately delivered, with 1 patient electively forgoing her final treatment. At a median follow-up of 16 months (range, 6-23 months), 3 patients have recurred at 8, 14, and 16 months from surgery. The median disease-free and overall survival have not been reached. FACT-O scores, as expected, demonstrated a significant decrease in the week following surgery (126 vs. 108, P b 0.01) but improved at or near the completion of therapy (108 vs. 113, P = 0.27). Conclusions: HIPC-therapy using carboplatin at 1,000 mg/m2 following optimal cytoreduction for ovarian cancer is feasible. Surgical complications were not observed, and postoperative AEs were largely within expected ranges. Consolidation using standard platinum-based regimens was feasible following HIPC, and preliminary survival data suggest efficacy. Further investigation of HIPC in the setting of debulkable cancer recurrence is warranted.
observation and 4 have enrolled in the maintenance Bev phase of the study; the remaining patient enrolled on GOG212. IP port complications and rectovaginal fistula resulted in the remaining 2 patients coming off of the study. Of note, the rectovaginal fistula was diagnosed in the middle of cycle 2 (she only received 1 dose of Bev) and was likely a complication from the patient’s initial surgery that included a rectosigmoid resection. All 7 patients who completed part A of the study currently have no evidence of disease. Conclusions: This phase I study was designed before the initiation of GOG 252. The MTD in this study was IP carboplatin AUC 6, IV paclitaxel 60 mg/m2, and bev 15 mg/kg. The majority of patients tolerated IP chemotherapy and dd paclitaxel with an acceptable adverse event profile. GOG 252 has completed enrollment, but consideration may be given to adjusting the dosing of this regimen in future trials.
doi:10.1016/j.ygyno.2013.04.356
Objective: In advanced ovarian carcinoma, there is concern that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to cytoreduction followed by chemotherapy. Choice of adjuvant regimen may become problematic in instances of poor response to NACT, even if optimal debulking is achieved. Class III beta-tubulin overexpression has been linked to hypoxia and chemoresistance through reduced binding of paclitaxel and modulation of prosurvival pathways. In this study, we described changes of class III betatubulin expression in response to NACT in relationship to oncologic outcome and comparatively between patients who underwent NACT vs. primary debulking. Methods: Patients with clinical stage IIIC/IV disease who received carboplatin/paclitaxel in neoadjuvant fashion or following primary debulking from 2003 to 2012 were identified retrospectively. Demographics/oncologic outcomes were recorded. Class III betatubulin expression in tumor/stroma was quantified by immunohistochemistry in matched formalin-fixed paraffin-embedded tissues representing pre-NACT biopsies and post-NACT specimens obtained at interval debulking. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantify expression in fresh-frozen tissues obtained from patients treated with NACT vs. primary debulking. Results: Patient characteristics for matched samples are provided in the Table. Among 22 paired specimens obtained before/after NACT, class III beta-tubulin expression decreased within stroma (P = 0.04) but was unchanged in tumor (P = 0.76) (Figure 1A). At time of interval debulking, reduced median overall survival (OS) was predicted by increased class III beta-tubulin staining by both tumor (high [2+,3+] vs. low [0,1+]: 596 days vs. not reached; HR 3.56; 95% CI 1.08,11.8; P = 0.04) and stroma (high [1+,2+,3+] vs. low
298 A phase I study of intraperitoneal carboplatin with intravenous paclitaxel and bevacizumab in patients with previously untreated epithelial ovarian carcinoma or primary peritoneal carcinoma D. O’Malley, E. Eisenhauer, G. McCann, R. Salani, F. Backes, L. Copeland, J. Fowler, D. Cohn. The Ohio State University, Columbus, OH. Objective: To determine the maximum tolerated dose (MTD) of intraperitoneal (IP) carboplatin, dose-dense (dd) intravenous (IV) paclitaxel, and bevacizumab (C/T/Bev) during the first 2 cycles of treatment in patients with chemo-naive epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (EOC). Methods: This was a phase I prospective study of patients with EOC with either optimal (≤1 cm maximum diameter) or suboptimal (N1 cm maximum diameter) residual disease following initial surgery. In part A, patients were treated with IP carboplatin/IV placlitaxel/IV bevacizumab (15 mg/kg) on day 1. IV paclitaxel was again administered on days 8 and 15 of 21-day cycles. Dose escalation first occurred with IP carboplatin from AUC 5 to 6, followed by dd paclitaxel (60, 70, 80 mg/ m2). Bev was held for cycle 1. Thus, MTD was based on toxicity from cycle 1 or 2. After presentation of GOG 213, the addition of maintenance Bev (part B) was optional after completion of 6 cycles. Results: A total of 9 patients were enrolled in the study. On the third dose level (IP carboplatin AUC 6, IV paclitaxel 70 mg/m2), 2 doselimiting toxicities (febrile neutropenia and 15-day delay secondary to neutropenia) occurred. Seven of nine patients completed all 6 cycles of C/T/Bev. After primary therapy, 2 patients elected for
doi:10.1016/j.ygyno.2013.04.357
Poster Area 4: Abstracts 299- 369 Ovarian Cancer (Translational Research/Basic Science, Palliative Care, Public Health, Quality of Life, and Rare Tumors
Ovarian Cancer (Translational Research/Basic Science) 299 Class III beta-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel D. Roque, N. Buza, M. Glasgow, E. Ratner, D. Silasi, M. Azodi, T. Rutherford, P. Schwartz, A. Santin. Yale University School of Medicine, New Haven, CT.
Objective: We investigated the significance of dose intensity on survival compared with treatment delay in adjuvant chemotherapy. Methods: Medical records of 429 patients diagnosed with epithelial ovarian cancer (EOC) between 2005 and 2011 were reviewed retrospectively. Relative dose intensity (RDI) was calculated with the ratio of delivered dose intensity to standard dose intensity. Multivariate analysis was performed to identify a prognostic significance of treatment delay and dose reduction to tumor recurrence. Results: Ninety-nine EOC patients received 6 cycles of postoperative adjuvant chemotherapy with paclitaxel and carboplatin. Mean values of RDI, treatment time intensity, and injected dose intensity were 93% (range, 70%-110%), 106% (range, 97%-127%), and 98% (range, 87%-110%), respectively. Most common causes of decreased RDI were neutropenia and thrombocytopenia. Median progression-free survival (PFS) of patients who received chemotherapy with b90% of dose intensity was 11 months compared with 21 months for patients who received N90% of dose intensity. In contrast with treatment time delay, dose intensity was an independent prognostic factor for tumor recurrence with multivariate analysis (P = 0.030, 95% CI 1.307208.203). Conclusions: Dose reductions and treatment delays are the main ways to achieve an RDI for patients with chemotherapy-induced toxicity. Maintaining more than 90% of dose intensity is a significant factor in prolonging PFS. doi:10.1016/j.ygyno.2013.04.353
295 Successful oxaliplatin salvage for recurrent ovarian cancer after carboplatin/cisplatin allergy S. Taylor, T. Beck, T. Krivak, K. Zorn, J. Kelley, R. Edwards. MageeWomen’s Hospital of UPMC, Pittsburgh, PA. Objective: Hypersensitivity reactions preclude platinum re-challenge for up to 44% of patients receiving second-line and higher carboplatin/ cisplatin salvage therapy. Our center has used oxaliplatin challenge for platinum hypersensitivity since 2006. The objective of this study was to evaluate our patient experience in recurrent or progressive ovarian or fallopian tube cancer with oxaliplatin salvage. Methods: This is a single-institution, retrospective chart review of all patients from 1995 to 2012 receiving oxaliplatin for treatment of recurrent or progressive ovarian or fallopian tube carcinoma. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval, prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. All patients who received oxaliplatin for 1 or more cycles were included. A response to therapy was determined after 2 or more cycles. Results: We identified 44 patients who received oxaliplatin as treatment for epithelial ovarian or fallopian tube carcinoma. All patients had prior carboplatin therapy and 38.6% (17/44) had prior cisplatin therapy. Platinum hypersensitivity reactions were seen in 52.3% (23/44). Patients received a median of 2 prior platinum-containing chemotherapy regimens and a median of 5 chemotherapy lines before oxaliplatin exposure. No grade 3 or grade 4 toxicities were noted. No patients had treatment delays for pancytopenia. Nausea and dysesthesias were controlled medically and were not dose-limiting. No platinum-associated toxicities, such as nephropathy or neuropathy, progressed on oxaliplatin therapy or were dose-limiting. Disease response was seen in 56.8% of patients, with a median reduction in CA-125 to 55.3% of the starting level. In patients who responded to therapy, the median nadir of CA-125 was 19.1% of the starting level. Of those patients who responded to oxaliplatin therapy, 42.3% had a prior platinum hypersensitivity reaction and were not candidates for other platinum-containing
e123
regimens. Patients were followed for a median of 15.5 months (range, 1-46 months) after initiation of oxaliplatin therapy. Conclusions: In our institution’s experience, oxaliplatin is well tolerated and should be considered for platinum challenge desensitization after carboplatin/cisplatin hypersensitivity with a reasonable chance of response. doi:10.1016/j.ygyno.2013.04.354
296 Platinum dosing for epithelial ovarian cancer: Is it appropriate to use actual body weight? J. Martin, M. Shah, B. Erickson, L. Daily, D. Pasko, C. Walters, J. Fauci, K. Bevis. University of Alabama at Birmingham, Birmingham, AL. Objective: Rates of obesity in the United States continue to rise. Historically, obese patients with ovarian cancer have received adjusted-dose (AD) chemotherapy due to concerns for increased toxicity without corresponding benefit. However, there is evidence that chemotherapy pharmacokinetics in obese patients differ from those in normal-weight patients, and dose restriction (DR) may lead to poorer outcomes. Recently published guidelines by the American Society for Clinical Oncology recommend using the patient’s actual, as opposed to ideal, body weight. We sought to determine the rate of DR in our epithelial ovarian cancer (EOC) patient population and if that influenced outcomes. Methods: We conducted a retrospective review of EOC patients diagnosed between 2004 and 2009 at a single institution. Demographic data, tumor characteristics, and primary treatment details, including chemotherapy dosing, were abstracted. Only women who received 4 or more cycles of intravenous platinum/taxane regimens were included. Patients were considered DR if their total platinum dose was b90% of that predicted based on actual body weight. Student’s T-test and chisquare analysis were used to compare variables as appropriate. Results: Of 211 patients who met inclusion criteria, 98 (46%) were platinum dose-restricted. On average, DR women received 25% less platinum than their actual body weight dose would have predicted. The mean body mass index (BMI) of DR women was 32.3 compared to 23.9 among appropriately dosed (AD) women (P b 0.01). The 2 groups were the same in regard to race, stage, debulking status, and histology, although DR women were significantly younger (60.0 vs. 65.5 years, P b 0.01). Progression-free survival (PFS) and overall survival (OS) were not different (PFS 24.1 vs. 22.66 months, P = 0.59; OS 34.1 vs. 35.4 months, P = 0.61). AD women with a BMI N30 had a significantly shorter OS compared to DR women with a BMI N30 (26.8 vs. 37.3 months, P = 0.03). These groups did not differ in terms of debulking status, stage, or histology. However, the AD/BMI N30 group were significantly older than the AD/BMI N30 group (70.6 vs. 59.7 years, P = 0.02). Conclusions: Obese patients with EOC commonly receive substantially lower doses of platinum when treated based on ideal body weight, but this does not appear to affect PFS or OS. However, older women with a BMI N30 have a significantly worse survival when dosed on actual body weight. This issue warrants further investigation. doi:10.1016/j.ygyno.2013.04.355
297 Hyperthermic intraperitoneal chemotherapy with carboplatin for recurrent epithelial ovarian cancer: A pilot study T. Sueblinvong1, P. Argenta1, M. Geller1, L. Downs1, A. Jonson1, L. Carson1, J. Ivy1, P. Judson Lancaster2. 1University of Minnesota, Minneapolis, MN, 2Moffit Cancer Center, Tampa, FL.
e124
Abstracts / Gynecologic Oncology 130 (2013) e1–e169
Objective: To evaluate the feasibility and tolerability of hyperthermic intraperitoneal carboplatin (HIPC) following secondary cytoreduction for recurrent, platinum-sensitive ovarian cancer. Methods: A single-institution prospective pilot study. Ten patients underwent secondary cytoreductive surgery followed by HIPC with carboplatin at 1,000 mg/m2. Consolidation (6 cycles) was with standard platinum-based regimens. Adverse events (AE) were monitoring according to CTCAE v4.0 guidelines. Quality of life was measured before surgery, within 1 week of HIPC-carboplatin, and at the conclusion of therapy using FACT-O tool. Results: Twelve patients were enrolled of which 2 were excluded (1 each for extra-abdominal disease identified before surgery and suboptimal cytoreduction). All 10 remaining patients received prescribed HIPC. There were no intraoperative complications or AEs attributable to HIPC therapy. Grade 1/2 nausea was the most common postoperative toxicity (6/10 patients), but this was managed with oral and/or antiemetics. Two patients had grade 4 postoperative neutropenia and thrombocytopenia, but only 1 experienced transient treatment delay. The median hospital stay was 5.5 days. A total of 69/70 (98%) planned chemotherapy doses were ultimately delivered, with 1 patient electively forgoing her final treatment. At a median follow-up of 16 months (range, 6-23 months), 3 patients have recurred at 8, 14, and 16 months from surgery. The median disease-free and overall survival have not been reached. FACT-O scores, as expected, demonstrated a significant decrease in the week following surgery (126 vs. 108, P b 0.01) but improved at or near the completion of therapy (108 vs. 113, P = 0.27). Conclusions: HIPC-therapy using carboplatin at 1,000 mg/m2 following optimal cytoreduction for ovarian cancer is feasible. Surgical complications were not observed, and postoperative AEs were largely within expected ranges. Consolidation using standard platinum-based regimens was feasible following HIPC, and preliminary survival data suggest efficacy. Further investigation of HIPC in the setting of debulkable cancer recurrence is warranted.
observation and 4 have enrolled in the maintenance Bev phase of the study; the remaining patient enrolled on GOG212. IP port complications and rectovaginal fistula resulted in the remaining 2 patients coming off of the study. Of note, the rectovaginal fistula was diagnosed in the middle of cycle 2 (she only received 1 dose of Bev) and was likely a complication from the patient’s initial surgery that included a rectosigmoid resection. All 7 patients who completed part A of the study currently have no evidence of disease. Conclusions: This phase I study was designed before the initiation of GOG 252. The MTD in this study was IP carboplatin AUC 6, IV paclitaxel 60 mg/m2, and bev 15 mg/kg. The majority of patients tolerated IP chemotherapy and dd paclitaxel with an acceptable adverse event profile. GOG 252 has completed enrollment, but consideration may be given to adjusting the dosing of this regimen in future trials.
doi:10.1016/j.ygyno.2013.04.356
Objective: In advanced ovarian carcinoma, there is concern that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to cytoreduction followed by chemotherapy. Choice of adjuvant regimen may become problematic in instances of poor response to NACT, even if optimal debulking is achieved. Class III beta-tubulin overexpression has been linked to hypoxia and chemoresistance through reduced binding of paclitaxel and modulation of prosurvival pathways. In this study, we described changes of class III betatubulin expression in response to NACT in relationship to oncologic outcome and comparatively between patients who underwent NACT vs. primary debulking. Methods: Patients with clinical stage IIIC/IV disease who received carboplatin/paclitaxel in neoadjuvant fashion or following primary debulking from 2003 to 2012 were identified retrospectively. Demographics/oncologic outcomes were recorded. Class III betatubulin expression in tumor/stroma was quantified by immunohistochemistry in matched formalin-fixed paraffin-embedded tissues representing pre-NACT biopsies and post-NACT specimens obtained at interval debulking. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantify expression in fresh-frozen tissues obtained from patients treated with NACT vs. primary debulking. Results: Patient characteristics for matched samples are provided in the Table. Among 22 paired specimens obtained before/after NACT, class III beta-tubulin expression decreased within stroma (P = 0.04) but was unchanged in tumor (P = 0.76) (Figure 1A). At time of interval debulking, reduced median overall survival (OS) was predicted by increased class III beta-tubulin staining by both tumor (high [2+,3+] vs. low [0,1+]: 596 days vs. not reached; HR 3.56; 95% CI 1.08,11.8; P = 0.04) and stroma (high [1+,2+,3+] vs. low
298 A phase I study of intraperitoneal carboplatin with intravenous paclitaxel and bevacizumab in patients with previously untreated epithelial ovarian carcinoma or primary peritoneal carcinoma D. O’Malley, E. Eisenhauer, G. McCann, R. Salani, F. Backes, L. Copeland, J. Fowler, D. Cohn. The Ohio State University, Columbus, OH. Objective: To determine the maximum tolerated dose (MTD) of intraperitoneal (IP) carboplatin, dose-dense (dd) intravenous (IV) paclitaxel, and bevacizumab (C/T/Bev) during the first 2 cycles of treatment in patients with chemo-naive epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (EOC). Methods: This was a phase I prospective study of patients with EOC with either optimal (≤1 cm maximum diameter) or suboptimal (N1 cm maximum diameter) residual disease following initial surgery. In part A, patients were treated with IP carboplatin/IV placlitaxel/IV bevacizumab (15 mg/kg) on day 1. IV paclitaxel was again administered on days 8 and 15 of 21-day cycles. Dose escalation first occurred with IP carboplatin from AUC 5 to 6, followed by dd paclitaxel (60, 70, 80 mg/ m2). Bev was held for cycle 1. Thus, MTD was based on toxicity from cycle 1 or 2. After presentation of GOG 213, the addition of maintenance Bev (part B) was optional after completion of 6 cycles. Results: A total of 9 patients were enrolled in the study. On the third dose level (IP carboplatin AUC 6, IV paclitaxel 70 mg/m2), 2 doselimiting toxicities (febrile neutropenia and 15-day delay secondary to neutropenia) occurred. Seven of nine patients completed all 6 cycles of C/T/Bev. After primary therapy, 2 patients elected for
doi:10.1016/j.ygyno.2013.04.357
Poster Area 4: Abstracts 299- 369 Ovarian Cancer (Translational Research/Basic Science, Palliative Care, Public Health, Quality of Life, and Rare Tumors
Ovarian Cancer (Translational Research/Basic Science) 299 Class III beta-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel D. Roque, N. Buza, M. Glasgow, E. Ratner, D. Silasi, M. Azodi, T. Rutherford, P. Schwartz, A. Santin. Yale University School of Medicine, New Haven, CT.