Chemotherapy of advanced ovarian cancer with 4'-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensity.

1990 ◽  
Vol 8 (4) ◽  
pp. 705-714 ◽  
Author(s):  
F Lévi ◽  
M Benavides ◽  
C Chevelle ◽  
F Le Saunier ◽  
F Bailleul ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Experimental Studies ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Clinical Response Rate ◽  
Survival Times ◽  
Gynecology And Obstetrics ◽  
Pathological Cr

The efficacy and toxicity of the new anthracycline, 4'-0-tetrahydropyranyl doxorubicin (THP) (50 mg/m2 intravenous [IV] bolus) in association with cisplatin (100 mg/m2 IV as a 4-hour infusion) was assessed in 31 patients with advanced ovarian carcinoma. Twenty-eight patients were assessable for toxicity among whom 25 were assessable for response (International Federation of Gynecology and Obstetrics [FIGO] stage IIIa, four patients; IIIb, 15 patients; IV, six patients). Nine patients had received prior treatment. Patients were randomized to receive schedule (sch) A (THP at 6 hours, then cisplatin from 16 to 20 hours) or sch B (THP at 18 hours, then cisplatin from 4 to 8 hours). Sch A was hypothesized as less toxic since THP was best tolerated in the late rest span and cisplatin near the middle of the activity span in experimental studies. The rate of clinical complete response (CR) was 52%, that of partial response (PR) was 12%, and the overall clinical response rate (CR plus PR) was 64% (sch A, 73%; sch B, 57%). Median progression-free survival and survival times were, respectively, 10 and 19 months. Of 12 patients in clinical CR evaluated at second-look laparotomy, four had a pathological CR (33%), and three had microscopic residual disease (MD). The overall rate of pathological CR was 16%. Sch A was associated with less neutropenia (P = .10), thrombocytopenia (P less than .01), anemia (P less than .01), and renal toxicity (P less than .05) than sch B. Of four patients withdrawn for toxicity, three were on sch B (one death). Mean dose intensities (DIs) of THP and cisplatin, respectively, decreased by 30% and 47% over the five initial courses. Such decrease was significantly more pronounced for sch B than for sch A in previously untreated patients (P from 2-way analysis of variance [ANOVA] less than .01). THP-cisplatin is active against advanced ovarian cancer, and its toxicities can be significantly decreased by dosing THP in the early morning and cisplatin in the late afternoon as compared with THP in the evening and cisplatin the next morning.

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

1996 ◽  
Vol 14 (2) ◽  
pp. 351-356 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
F Carnino ◽  
A Gadducci ◽  
R Algeri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Total Dose ◽  
Low Dose ◽  
Residual Disease ◽  
Randomized Study ◽  
Pathologic Complete Response ◽  
Dose Intensity ◽  
Clinical Response Rate ◽  
High Dose ◽  
Survival Times

PURPOSE The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

1986 ◽  
Vol 4 (6) ◽  
pp. 965-971 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
S Chiara ◽  
M R Sertoli ◽  
M G Daga ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Survival ◽  
Stable Disease ◽  
Residual Disease ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Second Look

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

A randomized trial of carboplatin versus iproplatin in untreated advanced ovarian cancer.

1991 ◽  
Vol 9 (7) ◽  
pp. 1131-1137 ◽  
Author(s):  
C Trask ◽  
A Silverstone ◽  
C M Ash ◽  
H Earl ◽  
C Irwin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Recurrent Disease ◽  
Advanced Ovarian Cancer ◽  
Figo Stage ◽  
Disease Treatment ◽  
Minor Response ◽  
Reduced Dose ◽  
Gynecology And Obstetrics ◽  
To Receive

Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent.

Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study.

1991 ◽  
Vol 9 (10) ◽  
pp. 1793-1800 ◽  
Author(s):  
J Grem ◽  
P O'Dwyer ◽  
P Elson ◽  
N Simon ◽  
D Trump ◽  
...  
Keyword(s):  
Clinical Response ◽  
Response Rate ◽  
Residual Disease ◽  
Eastern Cooperative Oncology Group ◽  
Dose Intensity ◽  
Complete Response ◽  
Clinical Response Rate ◽  
Hematologic Toxicity ◽  
Survival Times ◽  
Moderate Nausea

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.

scholarly journals Role of Lymphadenectomy During Interval Debulking Surgery Performed After Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Minjun He ◽  
Yuerong Lai ◽  
Hongyu Peng ◽  
Chongjie Tong
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Debulking Surgery ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Interval Debulking Surgery

ObjectiveThe role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS.MethodsWe retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS.ResultsIn 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease < 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease < 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS.ConclusionLymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

Long-term follow-up confirms a survival advantage of the paclitaxel–cisplatin regimen over the cyclophosphamide–cisplatin combination in advanced ovarian cancer

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 144-148 ◽  
Author(s):  
M. J. Piccart ◽  
K. Bertelsen ◽  
G. Stuart ◽  
J. Cassidy ◽  
C. Mangioni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Clinical Response Rate ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinically Significant

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European–Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin–paclitaxel regimen over cisplatin–cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

1992 ◽  
Vol 10 (5) ◽  
pp. 718-726 ◽  
Author(s):  
K Swenerton ◽  
J Jeffrey ◽  
G Stuart ◽  
M Roy ◽  
G Krepart ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Residual Disease ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Treatment Center ◽  
Clinical Response Rate ◽  
Time To Progression

PURPOSE Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

2004 ◽  
Vol 22 (13) ◽  
pp. 2635-2642 ◽  
Author(s):  
Sabino De Placido ◽  
Giovanni Scambia ◽  
Giovanni Di Vagno ◽  
Emanuele Naglieri ◽  
Alessandra Vernaglia Lombardi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Significant Difference ◽  
Grade 3

Purpose Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

scholarly journals Bevacizumab Combined with Platinum–Taxane Chemotherapy as First-Line Treatment for Advanced Ovarian Cancer: Results of the NOGGO Non-Interventional Study (OTILIA) in 824 Patients

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4739
Author(s):  
Jalid Sehouli ◽  
Alexander Mustea ◽  
Guelten Oskay-Özcelik ◽  
Maren Keller ◽  
Rolf Richter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Figo Stage ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
One Year ◽  
Oncology Practice ◽  
Taxane Chemotherapy

In the single-arm non-interventional OTILIA study, patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IIIB–IV ovarian cancer received bevacizumab (15 mg/kg every 3 weeks for up to 15 months) and standard carboplatin–paclitaxel. The primary aim was to assess safety and progression-free survival (PFS). Subgroup analyses according to age were prespecified. The analysis population included 824 patients (453 aged <70 years, 371 aged ≥70 years). At data cutoff, the median bevacizumab duration was 13.8 months. Grade ≥3 adverse events (AEs), serious AEs, and AEs leading to bevacizumab discontinuation were more common in older than younger patients, whereas treatment-related AEs were less common. Median PFS was 19.4 months, with no clear difference according to age (20.0 vs. 19.3 months in patients <70 vs. ≥70 years, respectively). One-year OS rates were 92% and 90%, respectively. Mean change from baseline in global health status/quality of life showed a clinically meaningful increase over time. In German routine oncology practice, PFS and safety were similar to reported randomized phase 3 bevacizumab trials in more selected populations. There was no notable reduction in effectiveness and tolerability in patients aged ≥70 years; age alone should not preclude use of bevacizumab-containing therapy. ClinicalTrials.gov: NCT01697488.

Management of retroperitoneal lymph nodes in advanced ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 7-10 ◽  
Author(s):  
N. F. Hacker ◽  
S. Valmadre ◽  
G. Robertson
Keyword(s):  
Ovarian Cancer ◽  
Lymph Nodes ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Free Survival ◽  
Systematic Lymphadenectomy ◽  
Clinically Normal ◽  
High Incidence ◽  
Very High

Autopsy studies have demonstrated a very high incidence of positive retroperitoneal lymph nodes in patients with advanced ovarian cancer, but the clinical management of these nodes has only recently been investigated. Several institutional studies had suggested an advantage to systematic removal of pelvic and paraaortic nodes in patients whose tumor was optimally cytoreduced in the peritoneal cavity. However, the only randomized prospective study revealed a 7-month benefit in progression-free survival for patients having systematic lymphadenectomy, but no benefit in terms of overall survival. Unless a future randomized trial shows evidence to the contrary, removal of clinically normal nodes should not be considered part of the standard care for patients with advanced ovarian cancer. Bulky nodes should be removed as part of the surgical aim of removing all macroscopic residual disease

Sign in / Sign up

Export Citation Format

Share Document