bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter randomized phase III trial of 3-weekly paclitaxel/platinum (PC3w) versus weekly paclitaxel/platinum (PCw) induction therapy followed by PC3w maintenance therapy in advanced epithelial ovarian cancer (EOC)
Authors: Burg M. E. , Janssen J. T. , Ottevanger P. B. , Kerkhofs L. G. , Valster F. , Stouthard J. M. , Onstenk W. , Termorshuizen F. , Verweij J. 
Published: August 2020

5538 Background: Response rates (RR) up to 50% were found with PCw in platinum resistant EOC. We compared the efficacy of first-line PCw induction therapy to PC3w. Methods: 270 patients (pts) with FIGO stage II-IV, Performance status (PS) 0–2 were randomly assigned to 3 x PC3w (P 175mg/m2 with either cisplatin [Cis] 75mg/m2 or carboplatin [Car] AUC 6) or 6 x PCw (P 90mg/m2 with either Cis 70mg/m2 or Car AUC 4, day 1,8,15 and day 29,36,43) followed by up to 6 cycles PC3w in both arms. Pts were stratified for FIGO stage, PS, tumor size and center. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were RR and toxicity. A total of 225 events were needed to detect a 10–13% absolute difference in PFS/OS with a power of 84% (one-sided). Results: 267 pts (134 TC-3w and 133 TCw) were eligible (3 pts wrong tumor type). Pt characteristics were well balanced; median age 58 years, serous 62%, residual disease >1cm 66%, FIGO stage II 7%, III 64%, IV 29%. Median dose-intensity for PC3w was: P 58(47–58) and Cis 25(22.5–25) mg/m2/w, Car 2(1.6–2) AUC/w, for PCw: P 60(36–60) and Cis 44.7(30–44.7) mg/m2/w and for Car 2.7(1,6–2,7) AUC/w. After a median follow-up of 39 months (m) (range 0.03 - 93.3m) 206 pts (77%) had progressed and 164 pts (61%) had died. Median PFS was 18m for TC3w and 19m for TCw, 5-year PFS was 20% and 18%, respectively (logrank test: p = 0.63). Median OS was 44m for TC3w and 45m for TCw, 5-year OS was 36% and 37%, respectively (logrank test: p = 0.87). RR after induction therapy in 176 pts with measurable disease was 72% for TC3w and 74% for TCw (p = 0.68). TCw was well tolerated. Grade 3/4 toxicity for TC3w vs. TCw was respectively, platelets 1.75% vs.1.55% (ns), WBC 5.5% vs. 8.7 (p = <0.0001), granulocytes 16.7% vs. 11.7% (p = <0.001) and delay 3% vs. 9% of the cycles. TCw induced less grade 2/3 muscular and joint pain (TC3w 6.3% and 3.5% vs. TCw 0.3% and 0.8% of the cycles) and less neurotoxicity (TC3w 6% vs. 1.6% of the pts in TCw). The other toxicities were similar in frequency and severity in both arms. Conclusions: TCw was well tolerated and had less granulocytopenia, neurotoxicity, and muscular and joint pain but did not yield benefit in terms of OS, PFS or RR. No significant financial relationships to disclose.
Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from ovarian cancer: A multiinstitutional study of 246 patients
Authors: Bereder J. , Glehen O. , Habre J. , Desantis M. , Cotte E. , Mounier N. , Ray-Cocquard I. , Karimdjee B. , Bakrin N. , Bernard J. , Benchimol D. , Gilly F. 
Published: August 2020

5542 Background: Optimal treatment of chemoresistant and recurrent ovarian cancer is debating with second line chemotherapies. For peritoneal carcinomatosis new treatment combining cytoreductive surgery with heated intraperitoneal per operative chemotherapy (HIPEC) may improve survival. Methods: Retrospective bicentric study of 246 patients with peritoneal carcinomatosis from ovarian cancer were performed to evaluate HIPEC and to identify prognostic factors. Peritoneal Cancer Index (PCI) assess tumor load and completeness cytoreductive score (CCS) was used to give quality of resection CC0 (no visible tumor), CC1 (persistent diffuse lesions < 2.5mm), CC2 (2.5mm < CC2 < 25mm) and over CC3 status. HIPEC is performed with platinum based regimen at 42°C. Endpoint was survival. Kaplan-Meier survival curve was fitted to the data. Cox's regression model was used for multivariate survival analysis. Results: The study included 268 procedures in 246 patients from 1991 to 2008. 206 procedures were performed in 184 patients with recurrence (Group 1) and 62 in chemoresistant patients (Group 2). After completion of resection the allocation of CCS was CC0 = 164, CC1 = 83, CC2 = 15, and CC3 = 5. Only 1 patient died in post operative course and procedure related morbidity rate was 12%. 5 years overall and free survival were respectively 35 % and 10%. Median overall survival was 49 months and the median disease free survival was 13 months. There was no difference between group 1 and 2 for survival. Independent prognostic factors for survival were the carcinomatosis extent, the completeness of cytoreductive surgery (HR = 2.26 IC95 [1.3–3.91]), performance status (HR = 4.3 IC95 [1.23–14.4]) and redo procedure (HR = 0.9 IC95 [0.001–0.9]). Conclusions: Hipec is a standardized and reproducible feasible method. Less extensive disease and the quality of cytoreduction remain an independent factor of better outcome. Morbidity is acceptable. To date in selected patients, HIPEC allows to reach the longest median time survival in recurrent peritoneal carcinomatosis from ovarian cancer. No significant financial relationships to disclose.
Pegylated liposomal doxorubicin (PLD) with bevacizumab (B) in second-line treatment of ovarian cancer (OC): Pharmacokinetics (PK), safety, and preliminary outcome results
Authors: Muggia F. M. , Boyd L. , Liebes L. , Downey A. , Muller C. , Pothuri B. , Blank S. , Rutledge T. , Fishman D. , Verschraegen C. 
Published: August 2020

5548 Background: PLD activity in platinum-resistant OC is modest. B, with its activity in platinum(Plat)-sensitive and Plat-resistant patients (pts), has not been combined with PLD. PLD intratumoral concentrations, if affected by B, might be reflected in PLD PK. This phase II study of PLD + B was started in 2007 to accrue 48 pts, unless 4 serious (> grade 3) adverse events (AEs) supervened. Methods: Improvement in progression-free survival (PFS) at 6 m from 25 to 40% at 6 m in Plat-resistant OC is primary endpoint. PK of PLD alone at 1h, d 7 and d 21 (cycle 1) vs with B (cycle 2), safety, and response rates (RECIST and CA125 criteria) were secondary endpoints. Dosing: PLD 30 mg/m2 followed by B 15 mg/kg on cycles 2–7 (with option to continue) d 1 every 3 w. Pts recurring within 6 m of platinum-based treatment for OC after < 3 prior regimens (but no PLD or B) were eligible. Exclusions: bowel obstruction, prior perforation, uncontrolled hypertension, or vascular disease. Hematologic, mucocutaneous and renal toxicities were evaluated prior to each cycle, MUGA scans every third cycle; disease status by CA125 and/or RECIST every third cycle. Results: 21 of 24 pts enrolled to date are evaluable. Median age is 65, range 52–83; most had 2 prior chemotherapy regimens. Median 6 (range 3–12) cycles were given with 6 off study with progression at 3–7 cycles. RECIST and CA125 responses are under review; in 11 pts with baseline CA125 of > 40 IU/mL, median increase was 31% by cycle 2; later falling to -57%. AEs did not exceed grade 3; hand-foot syndrome led to PLD dose reduction in 8 pts (33%); asymptomatic decreases in left ventricular ejection fraction (LVEF) >10% in 3 pts were noted, with treatment discontinuation in 1. The mean (±SEM) secondary PK parameter estimates for Cmax, AUC, and elimination half life were 4.5 ± 0.5 ug/mL, 651.7 ± 61 ug/mL x h, and 93.3 ± 19.7 h, respectively. Conclusions: Cycles 1 and 2 PLD PK do not differ. PLD + B is tolerable with PLD dose modifications. Declines in LVEF in 1 institution have uncertain causality. Midway into the trial, safety and time on study encourage completion for study primary endpoint. [Table: see text]
Oxaliplatin plus continuous infusion topotecan: First stage of an ongoing phase II study for recurrent ovarian cancer: A New York Cancer Consortium study (#N01-CM62204)
Authors: LaNatra N. , Hochster H. , Muggia F. , Blank S. V. , Curtin J. , Fishman D. , Shapira I. E. , Goldberg G. L. , Parise S. , Tiersten A. 
Published: August 2020

5556 Background: Topoisomerase-1 inhibitors and platinums are active in ovarian cancer. Our prior series described infusional topotecan as less myelosuppressive than bolus and more easily combined with oxaliplatin than cisplatin. An NYU phase I study of the combination in previously treated ovarian cancer patients (pts) showed promising activity and good tolerability (Hochster H, Gynecol Oncol 2008). Methods: Ovarian cancer pts treated with 1–2 prior regimens (1 platinum/taxane regimen, no topotecan) were treated with oxaliplatin 85 mg/m2 day 1, 15 and topotecan (0.4 mg/m2/day) continuous infusion x 14 days every 4 weeks (wks). Platinum resistant (stratum I = 10) and sensitive (stratum II = 17) pts are included in this two-stage trial (n = 52) to evaluate overall response rate (ORR) and toxicities. Results: From January 2006 to November 2008, 27 pts entered. Median age was 61 (37–79). Fifteen pts had 1 prior regimen and 12 pts had 2. Five pts discontinued before 2 cycles (3 for predefined toxicity, 2 by pt/physician choice). 102 cycles of chemotherapy were given (median 4, [1–6]). Grade 3/4 toxicities included thrombocytopenia (37% grade 3, 19% grade 4), neutropenia (37% grade 3, 11% grade 4), anemia (15% grade 3), neuropathy (7% grade 3), diarrhea (4% grade 3), transaminitis (4% grade 3), and fatigue (7% grade 3). Twenty-one pts had day 15 oxaliplatin held, 10 pts required dose reductions, and 21 pts had treatment delays mainly from thrombocytopenia. No pts had neutropenic fever. Twenty-one pts are now evaluable. Stratum I had 1 complete and no partial responses, 5 pts with stable disease and 2 with progressive disease. Stratum II had 3 complete and 6 partial responses, 4 pts with stable disease and none progressed. Median response duration is 41 wks (17–62); median duration of stable disease is 17 wks (4–70). Conclusions: Excluding thrombocytopenia, tolerance to this regimen confirms phase I results. In pts with creatinine clearances (CrCl) < 60 ml/min, the incidence of grade 3/4 thrombocytopenia was 75% versus 35 % for pts with CrCl > 60 ml/min. Pts with CrCl of 40–60 ml/min will now start topotecan 0.3 mg/m2/day x 14 days. Reaching our predefined ORR of at least 30% for stratum II and 20% for stratum I, the second stage of accrual has begun. [Table: see text]
Weekly paclitaxel (wP) as single agent or in combination with weekly topotecan (wT) or carboplatin (C) in patients with resistant ovarian cancer (ROC): The phase II CARTAXHY randomized trial from GINECO
Authors: Gladieff L. , Lortholary A. , Largillier R. , Weber B. , Alexandre J. , Durando X. , Slama B. , Dauba J. , Paraiso D. , Pujade-Lauraine E. 
Published: August 2020

5557 Background: For ROC patients (pts) with early progression during or after (< 6 months) platinum and 3 weekly P, use of single non-platinum agent including wP is standard (Kristensen G, et al. J Clin Oncol 26: 2008 abstr 5508). Few randomized trials have explored combination therapy in this setting. Methods: Pts with ROC after a first or second line including a platinum and a taxane were randomized to receive wP (80 mg/m2/week) alone or in combination with wT (3mg/m2/week) or C (AUC 5 every 4 weeks). The primary end-point was the comparison of progression-free survival (PFS) between single non-platinum agent and combination therapy (wP+wT or wP+C). Secondary objectives included safety, QoL, response rate (RR) and overall survival. Results: From April 2004 to August 2008, 165 pts were accrued (wP 57, wP+wT 57, wP+C 51). Median number of cycles and P dose-intensity (mg/m2/week) was 4.6 and 70, 4.2 and 63 in monotherapy and combination therapy arms respectively. Non-hematological toxicity was not different between the arms, except an excess of hypersensitivity reactions in the wP+C arm. Grade 3–4 neutropenia (48 vs 13% of pts), and anemia (24 vs 6%) were more frequent in combination therapy than in single agent arm and similar with wT or C combination. Febrile neutropenia was experienced by 5 pts treated with combination therapy. Discontinuation from drug treatment was more frequent with combination therapy (24% of pts) than with monotherapy (4%), mainly due to hematotoxicity. RR was 34, 38 and 39% for wP, wP+wT and wP+C respectively. Median PFS of pts treated with single agent (112 days) was not significantly different from those treated with combination therapy (149 days) (p = 0,62) and was similar in wP+wT (152 days) or wP+C (146 days) arms. Treatment with single non-platinum agent or combination therapy was not found an independent parameter when added to a Cox model including prognostic variables. Conclusions: Combination therapy (CT) in platinum resistant ovarian cancer was found more toxic than weekly paclitaxel and the PFS advantage from CT was not statistically significant. No significant financial relationships to disclose.
A phase II trial of voreloxin in women with platinum-resistant ovarian cancer
Authors: Hirte H. W. , McGuire W. , Edwards R. , Husain A. , Hoskins P. , Michels J. , Matulonis U. , Sexton C. , Michelson G. 
Published: August 2020

5559 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Clinical activity has been observed in ovarian cancer and AML. Results are reported from a fully enrolled phase II study of 3 dose levels of single agent voreloxin in patients (pts) with 1° or 2° platinum-resistant or refractory ovarian cancer. Methods: Pts may have received ≤ 3 prior platinum regimens plus one additional non-platinum regimen. PS of 0–1 was required. Voreloxin regimens: Cohort A 48 mg/m2q3weeks (wk) (N = 65), Cohort B 60 mg/m2q4wk (N = 35), and Cohort C 75 mg/m2q4wk (N = 35) by short IV infusion. BRCA status is reported by pt consent. Results: Cohort A: 2CRs, 5PRs; ORR 11%; median PFS 82 days (52–98 days 95%CI); Cohort B: 1CR, 3PRs; ORR 11%, median PFS too early to evaluate (TETE); Cohort C - TETE. Cohort A: Febrile neutropenia (FN) incidence was low (8%). Other common G3 or G4 AEs reported (≥ 5%) were fatigue (14%) and nausea (5%). Dose delays or reductions (40%) occurred typically at Cycle 1, largely due to neutropenia. Cohort B: Dose was increased to 60 mg/m2 and dosing interval was lengthened to 4 wk, maintaining dose intensity (DI) and allowing adequate time for marrow recovery. ANC dosing criterion was changed from ANC ≥ 1,500 to ≥ 1,000. There was a marked decrease in dose delays and reductions (14%) with only 3% incidence of FN. Common G3 or 4 AEs reported (≥ 5%) were fatigue (11%) and nausea (5%). The safety profile supported further dose escalation to 75 mg/m2q4wk (Cohort C- DI increased by 25%). Data are TETE. Conclusions: Preliminary data suggest Cohorts A and B have similar safety and efficacy profiles as anticipated based on comparable DI. Fewer dose reductions and delays occurred in Cohort B, due to revised dosing criteria and increased cycle length to 4 wk. Accrual to Cohort C is complete. Efficacy and safety data for all cohorts will be reported. [Table: see text]
A phase II study evaluating the safety and efficacy of patupilone in patients with platinum refractory/resistant ovarian, primary fallopian, or peritoneal cancer
Authors: Smit W. M. , Sufliarsky J. , Werner T. L. , Dizon D. , Wagnerova M. , Hirte H. W. , Delaney R. , Li J. , Weber D. , Schellens J. H. 
Published: August 2020

5563 Background: Patients with ovarian cancer that relapse or recur within 6 months after platinum plus taxane therapy have a poor prognosis. Patupilone, a natural epothilone isolated from myxobacterium, is a microtubule targeting agent that was found to be safe and well tolerated, with clinical activity in refractory or resistant ovarian cancer. Methods: Patients were treated with a dose of patupilone 10 mg/m2, given intravenously over 10–20 minutes once every 3 weeks, which was found safe in a previous phase I study. Results: Total 113 women enrolled and 112 were treated. The median age was 56 years (range 18–85 years), and 11 % had WHO Performance Status (PS) of 2. Most patients (104) had ovarian cancer, while 5 were peritoneal and 2 each of fallopian or other origin. All patients had received prior platinum and taxane, and 50% had progressed in less than 3 months after prior platinum therapy. Patients received a median of 4 cycles (range 1–16) of patupilone with median average dose per cycle of 9.97 mg/m2, resulting in a median dose intensity of 100%. The most common grade 3/4 toxicity was diarrhea (21%/3%), fatigue (10%/1%), intestinal obstruction (5%/3%), anorexia (5%/1%), and vomiting (8%/0%). About 38% patients developed neuropathy, which was mostly grade 1 (in 22%), with only 4% patients at grade 3. A total of 6 patients (5.4%) discontinued due to serious adverse event. There were 4 (3.6%) deaths on study, none of which were considered treatment related. The best overall response rate (by RECIST criteria) was 7.1% (95% CI: 3.0%, 14.0%) with no patient having complete response and 8 patients with partial response. Also, 46 patients (41%) had stable disease and 39 (34.8%) progressed, while response was unknown or could not be evaluated in 19 patients. The median PFS is 2.5 months (95% CI: 1.4, 3.5), and median overall survival is 11.2 months (95% CI: 8.3, 14.9), with 33% patients censored. Conclusions: Patupilone 10mg/m2 administered at q3wk was safe and well tolerated. It showed promising activity in patients with refractory/resistant ovarian cancer. [Table: see text]
Phase I feasibility study of carboplatin plus capecitabine followed by maintenance capecitabine in patients (pts) with recurrent platinum-sensitive epithelial ovarian cancer (EOC)
Authors: Montes A. , Sandhu S. K. , Rothermundt C. , Coombes I. , A'Hern R. , Keyzor C. , Thomas A. , Kaye S. , Gore M. 
Published: August 2020

5564 Background: In a previous study, we noted a response rate (RR) of 61% for the 3 drug combination of carboplatin, epirubicin and capecitabine in platinum-sensitive recurrent EOC. This combination however resulted in excessive grade (G) 3–4 haematological toxicity (55%) (BJC 2006; 94:74). The current trial therefore assessed the feasibility and efficacy of the 2 drugs, carboplatin and capecitabine as second- or third-line treatment. Methods: Pts were administered carboplatin (AUC5) day 1 and capecitabine at a starting dose of 750 mg/m2 bd, days 1–21, q21 (dose level 1). The capecitabine dose was deescalated to 625 mg/m2 (dose level -1) and 500 mg/m2 (dose level -2) according to toxicity. Pts with an objective response or stable disease received maintenance capecitabine (at the same dose level) for up to 12 months or until progression. Responses were assessed with RECIST criteria and CA-125. Results: 19 of the 20 pts enrolled were evaluable for toxicity and response. Dose-limiting toxicity was observed at dose level 1 (G3 fatigue, G3 diarrhoea, G3 neutropenia of > 14 days; n = 3/5), dose level -1 (G3 angina (n = 2), G3 vomiting, G3 palmar plantar erythema; n = 4/7) and dose level-2 (diarrhoea / fatigue; n = 1/7). One patient had a G3 carboplatin hypersensivity reaction. 8 pts received maintenance capecitabine which was well tolerated. The overall RR was 53% with 10 partial responses and 5 stable diseases. The median progression free survival (PFS) was 6.5 months (m) and the 6mPFS was 63% with 2 pts currently ongoing treatment. The median PFS on maintenance was 3.2 m. Conclusions: The combination was well tolerated at the recommended phase II dose of carboplatin (AUC 5) and capecitabine (500 mg/m2 bd) with partial responses in over half of the cases. [Table: see text]
Cost-effectiveness of zoledronic (ZOL) acid plus endocrine therapy (ET) in premenopausal women with early breast cancer (EBC) from a Canadian perspective
Authors: Ougari K. E. , Taneja C. , Sofrygin O. , Kaura S. , Delea T. 
Published: August 2020

557 Background: The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of 3 years (yrs) of treatment with goserelin in combination with ET (anastrozole or tamoxifen) with or without ZOL 4 mg q6 mos in 1,803 premenopausal women with EBC (median age 45 yrs). After a median follow-up of 47.8 mos (max 84 mos), risk of disease-free survival (DFS) events was reduced by 36% (HR = 0.64; p = 0.01) in patients (pts) who received ZOL (ZOL+ET) compared with those who did not (ET). Methods: A Markov model was used to estimate the cost per quality adjusted life years (QALYs) gained of 3 years treatment duration of ZOL+ET versus ET-only in premenopausal women with EBC based on results of the ABCSG-12. A Canadian healthcare system perspective and a lifetime timeframe were used. Outcomes and cost of breast cancer recurrence were based on recent published studies. Results were generated under 2 scenarios regarding duration of benefit (reduction in risk of recurrence) with ZOL: (1) Benefits persist to maximum follow-up in ABCSG-12 (trial benefit); (2) Benefits persist until death (lifetime benefit). Results: The cost of 3 years of ZOL (medication and administration) is 4 191 $CDN. Under the lifetime benefit scenario, 73% of these costs are offset by savings in the cost of recurrences. Under the trial benefit scenario, 12% are offset. QALYs gained are 1.63 yrs and 0.52 yrs under the lifetime and trial benefit scenarios respectively; cost-effectiveness is 1 122 $CDN and 3 675 $CDN per QALY gained respectively, which is well below the 50 000 $CDN per QALY threshold frequently used to assess whether therapies are cost-effective. Conclusions: The combination of ZOL + ET is a cost-effective use of healthcare resources from a Canadian healthcare system perspective. [Table: see text]
Antiangiogenic therapy for granulosa cell tumors of the ovary
Authors: Tao X. , Sood A. K. , Deavers M. T. , Schmeler K. M. , Nick A. M. , Coleman R. L. , Gershenson D. M. , Brown J. 
Published: August 2020

5574 Background: Sex-cord stromal ovarian tumors (SCSTs) tend to respond poorly to chemotherapy agents. Therefore, we examined the clinical efficacy of bevacizumab with or without concurrent chemotherapy and evaluated the angiogenic characteristics of these patients’ tumors. Methods: We conducted an IRB-approved retrospective review of all patients with SCSTs seen at our institution from February 2004 to October 2008. Eligible patients underwent pathologic confirmation and clinical evaluation, and received bevacizumab. VEGF and CD31 immunohistochemical staining (IHC) was performed when tissue was available; microvessel density (MVD) was measured based on CD31 counts. Results: We identified 8 eligible patients treated with bevacizumab. Of these, 7 had adult granulosa cell tumors (GCT) and one had a juvenile GCT. Of the 8 patients, 4 had early stage disease (I or II), 2 had advanced stage disease (III), and 2 were unstaged. All patients were treated for recurrent disease and had been previously treated with cytotoxic chemotherapy, with a median of 3.5 prior regimens (range, 1–6). Of the 8 patients, one patient had a complete clinical response, 2 patients had a partial response, 2 patients had stable disease, and 3 patients progressed, yielding a response rate of 38% and a clinical benefit rate of 63%. The median progression-free survival (PFS) was 7.2 months and the overall survival (OS) was not reached at a median follow-up after starting bevacizumab of 23.6 months. Of the 8 patients, 5 had tissue available for IHC. VEGF expression was noted at some level in all samples; overexpression was present in 1 of the 5 patients (upper tertile of score), and moderate expression was observed in 3 of the 5 patients (middle tertile). VEGF overexpression correlated with shorter PFS (p = 0.006) and shorter overall survival (p = 0.02). High MVD (>12.3 per previous data based on ROC analysis) was present in 3 of the 5 patients, and correlated with VEGF overexpression (p = 0.007) and shorter overall survival (p = 0.004). Conclusions: Anti-VEGF therapy is highly effective in patients with ovarian granulosa cell tumors. On the basis of these observations, a prospective trial has now been initiated using single agent bevacizumab in patients with recurrent disease. No significant financial relationships to disclose.