Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study.

1998 ◽  
Vol 16 (6) ◽  
pp. 2233-2237 ◽  
Author(s):  
P Hoskins ◽  
E Eisenhauer ◽  
S Beare ◽  
M Roy ◽  
P Drouin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Randomized Study ◽  
Recurrent Ovarian Cancer ◽  
S Phase ◽  
Randomized Phase Ii ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

PURPOSE As topotecan is S-phase-specific, its efficacy is likely schedule-dependent. Therefore, a randomized study using a "pick the winner" design was undertaken to compare two schedules in patients with recurrent ovarian cancer. PATIENTS AND METHODS Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy, one of which had to be platinum-containing, were randomized to either topotecan 1.5 mg/m2 intravenously (i.v.) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m2 as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm). RESULTS Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to 41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to 16%) (P = .026). The regimens were not equitoxic, with 94% of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B. CONCLUSION The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen.

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients

1989 ◽  
Vol 23 (5) ◽  
pp. 323-328 ◽  
Author(s):  
Nicoletta Colombo ◽  
James L. Speyer ◽  
Michael Green ◽  
Renzo Canetta ◽  
Uziel Beller ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Hematologic Toxicity ◽  
Previously Treated Patients ◽  
Previously Treated

Pentostatin and Cyclophosphamide: An Effective New Regimen in Previously Treated Patients With Chronic Lymphocytic Leukemia

2003 ◽  
Vol 21 (7) ◽  
pp. 1278-1284 ◽  
Author(s):  
Mark A. Weiss ◽  
Peter G. Maslak ◽  
Joseph G. Jurcic ◽  
David A. Scheinberg ◽  
Timothy B. Aliff ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response Rate ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Severe Nausea ◽  
Treatment Regimens ◽  
Purine Analogs ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

Purpose: Purine analogs and alkylators are important agents in the treatment of chronic lymphocytic leukemia (CLL). Previously, combinations of fludarabine and chlorambucil were abandoned because of increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin may be least myelosuppressive. We hypothesized that combining pentostatin with cyclophosphamide would have less myelotoxicity than combinations using other purine analogs. Patients and Methods: We studied 23 patients with previously treated CLL. All patients received pentostatin 4 mg/m2. Seventeen patients received cyclophosphamide 600 mg/m2, and six patients received cyclophosphamide 900 mg/m2. Both drugs were administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median number of prior treatment regimens was three (range, one to five) with 13 patients (57%) refractory to prior fludarabine therapy. Results: The cyclophosphamide 900 mg/m2 dose level was associated with moderate to severe nausea, and we chose cyclophosphamide 600 mg/m2 as the dose for further study. There were 17 responses (74%; 95% confidence interval, 63% to 85%), including four complete responses. The response rate was 77% in fludarabine-refractory patients. Myelosuppression was acceptable with grade 3/4 neutropenia and thrombocytopenia, seen in 35% and 30% of patients, respectively. The relative sparing of thrombopoiesis can be seen in that only one patient (5%) with an initial platelet count of more than 20,000 required platelet transfusions while receiving therapy. Conclusion: Pentostatin 4 mg/m2 with cyclophosphamide 600 mg/m2 is safe and effective in previously treated patients with CLL. On the basis of these results, we are currently studying pentostatin, cyclophosphamide, and rituximab (PCR) therapy in patients with CLL.

A phase II study of irinotecan combined with S-1 in patients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy

2019 ◽  
Vol 29 (3) ◽  
pp. 474-479
Author(s):  
Seiji Mabuchi ◽  
Eriko Yokoi ◽  
Kotaro Shimura ◽  
Naoko Komura ◽  
Yuri Matsumoto ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Cervical Cancer ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Grade 3

ObjectivesWe conducted a phase II study to investigate the efficacy and toxicities of irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.MethodsPatients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy were enrolled. Irinotecan (150 mg/m2) was administered intravenously over the course of 90 min on day 1, and S-1 (80 mg/m2) was given orally in two divided doses from days 1 to 14 of a 21 day cycle. The primary endpoint of this phase II study was response rate. Secondary endpoints included safety, progression free survival, and overall survival.ResultsA total of 19 patients were enrolled and treated. The response rate was 29.4%. Grade 3–4 hematologic toxicities were observed in three patients (15.7%). The only grade 3–4 non-hematologic toxicity observed was grade 3 diarrhea. The median progression free survival and overall survival were 3 months and 9 months, respectively.ConclusionS-1 plus irinotecan in a 3 weekly setting is safe and active in women with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy. Future corroborative clinical studies are warranted.

Efficacy and safety results from GEICO 1205, a randomized phase II trial of neoadjuvant chemotherapy with or without bevacizumab for advanced epithelial ovarian cancer

2019 ◽  
Vol 29 (6) ◽  
pp. 1050-1056 ◽  
Author(s):  
Yolanda Garcia Garcia ◽  
Ana de Juan Ferré ◽  
Cesar Mendiola ◽  
Maria-Pilar Barretina-Ginesta ◽  
Lydia Gaba Garcia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Debulking Surgery ◽  
Randomized Phase Ii ◽  
Interval Debulking Surgery ◽  
Grade 3 ◽  
Macroscopic Response

BackgroundBevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery.ObjectiveTo evaluate neoadjuvant bevacizumab in a randomized phase II trial.MethodsPatients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery.ResultsOf 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery.ConclusionsAdding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.

A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer

2008 ◽  
Vol 18 (3) ◽  
pp. 400-406 ◽  
Author(s):  
J. D. Wright ◽  
A. A. Secord ◽  
T. M. Numnum ◽  
R. P. Rocconi ◽  
M. A. Powell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Response ◽  
Response Rate ◽  
Single Agent ◽  
Chylous Ascites ◽  
Recurrent Ovarian Cancer ◽  
Cytotoxic Agent ◽  
Combination Group ◽  
Factors Associated ◽  
Grade 3

While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3–5 toxicities occurred in 15 (24%) patients, including grade 3–4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3–5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy

A phase I study of modified irinotecan (CPT-11) plus cisplatin (CDDP) [m-IP] against paclitaxel/carboplatin [TC] -resistant and recurrent ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13015-13015
Author(s):  
T. Suzuki ◽  
M. Morishita ◽  
M. Matsuura ◽  
T. Fujimoto ◽  
R. Tanaka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Hematological Toxicity ◽  
Prior Chemotherapy ◽  
Level 3 ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

13015 Background: CPT-11/CDDP is effective regimen for ovarian cancer. Particularly against ovarian cancer resistant to prior chemotherapy, a 40% response rate was reported (Sugiyama T Cancer Letters, 1998). However, every 4 weeks treatment with CPT-11 day 1, 8, and 15, administration on day 15 was skipped in about 60% due to toxicity, and the relative dose intensity of IP was 66.7% in non-small cell lung cancer (Saito H Am J Clin Oncol 2006). We planed Phase I study, in consideration of the effect of prior chemotherapy in TC-resistant ovarian cancer, a modified CPT-11 (day 1, 8) and CDDP (day 1) for every 4 weeks treatment (m-IP). The aim of this study conducted to examine the dose limiting toxicity (DLT), to evaluate the maximum tolerated dose (MTD), and define the recommended dose (RD) for a phase II study. Methods: Patients with TC-resistant ovarian cancer having a PS 0–1, age 30–75 years, normal organ functions, and written informed consent. CPT-11 was administered intravenously over 90 minutes on day 1 and day 8, plus CDDP was day 1, repeated every 4 weeks. The dose escalation schedule was defined: Doses of CPT-11/CDDP (mg/m2) were 60/60 at level 1, 70/60 at level 2 and 70/70 at level 3. DLT were determined as Grade 4 hematological toxicity and = Grade 3 non-hematological toxicity occurred, and when dosing on day 8 was delayed for more than 8 days due to toxicity. Results: Nine patients were enrolled (level 1/2/3: 3/3/3). DLTs, at level 1 and 2, no patients developed. At level 3, grade 3 nausea and vomiting and delayed treatment on day 8 due to anorexia, were observed in all of 3 patients. Therefore, MTD was determined to be level 3 and RD was determined to be level 2 (CPT-11: 70mg/m2, CDDP: 60mg/m2). Major =Grade 3 toxicities observed were leukopenia, neutropenia, nausea, and vomiting. No Grade 4 hematological toxicities were observed. Diarrhea was mild. Antitumor effect at RD was observed in 1 patient with CR, 1 patient with PR and 1 patient with PD. Conclusions: The MTD of m-IP was CPT-11 70mg/m2 and CDDP 70mg/m2 (level 3), the RD was CPT-11 70mg/m2 and CDDP 60mg/m2 (level 2). Preliminary response are promissing associated with tolerable toxicity for TC-resistant and recurrent ovarian cancer. A Phase II study is currently conducted. No significant financial relationships to disclose.

A phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9014-9014 ◽  
Author(s):  
Lyudmila Bazhenova ◽  
Mary Weber Redman ◽  
Scott N. Gettinger ◽  
Fred R. Hirsch ◽  
Philip C. Mack ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Randomized Study ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Grade 5 ◽  
Secondary Endpoints ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

9014 Background: Lung-MAP is a master protocol for patients (pts) with stage IV previously treated SqNSCLC. S1400I enrolled pts who were not eligible for a biomarker-matched sub-study. Methods: S1400I is phase III randomized trial for immunotherapy-naïve patients with ECOG 0-1 not selected by PD-L1 expression. Pts were assigned 1:1 to nivolumab and ipilimumab (N+I) vs nivolumab (N). N was given at 3 mg/kg q 2w, I was given at 1 mg/kg q 6w. The primary endpoint was overall survival (OS). Secondary endpoints: investigator-assessed progression-free survival (IA-PFS), response by RECIST 1.1, and toxicity. Results: From December 18, 2015 to April 23, 2018, 275 pts enrolled and 252 determined eligible (125 N+I and 127 N). The study was closed for futility at an interim analysis. Baseline characteristics were similar across arms. mOS was 10.0 m (8.0-12.8) and 11.0 m (8.2-13.5) for N+I and N. HR 0.97 (0.71-1.31), p 0.82. mPFS was 3.8 m (2.3-4.2) and 2.9 m (1.8-3.9) for N+I and N. HR 0.84 (0.64-1.09), p 0.19. Outcomes based on PD-L1 and TBM subsets are shown in table. Response rates were 18% (12-25%) and 17% (11-24%) for N+ I and N. Median follow up for patients still alive was 17.4 m. Grade ≥3 treatment-related AEs occurred in 48(39%) of pts on N+I vs 38(31%) on N. irAE reported in 39% of pts on N+I and 34% of patients on N. Drug-related AEs led to discontinuation in 25% and 16% of pts on N+I and N. There were 5 grade 5 AE in N+I arm and 1 in N arm. Conclusions: S1400I failed to show improvement in outcomes with N+I. Study was closed for futility at interim analysis. Toxicities were not different between two arms. Clinical trial information: 02785952. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document