Gemcitabine Plus Carboplatin Compared With Carboplatin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer: An Intergroup Trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG
Jacobus PfistererMarie PlanteIgnace VergoteAndreas du BoisHal W. HirteÁngel J. LacaveUwe WagnerAnne StähleGavin StuartRainer KimmigS. OlbrichtTien LeJanusz EmerichWalther KuhnJ. BentleyChristian JackischHans‐Joachim LückJustine RochonAnnamaria H. ZimmermannElizabeth A. Eisenhauer
743
Citation
25
Reference
10
Related Paper
Citation Trend
Abstract:
Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients.Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS).Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted.Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.Keywords:
Carboplatin
Regimen
Gemcitabine (GEM) has been reported to be an active agent in pancreatic cancer. Single-agent gemcitabine is currently the chemotherapy standard, although response rate being modest. Therefore, studies over the past few years have focused on gemcitabine-based combination chemotherapy and recent applications have included the use of a fixed-dose rate regimen. The purpose of this study is to evaluate the feasibility and efficacy of a new regimen, a fix-dose rate infusion of low-dose GEM (FRI regimen), as compared with a standard infusion (SI regimen) in patients with pancreatic cancer. 27 patients were enrolled (12 patients were resectable and 15 patients were unresectable). This FRI regimen consisted of gemcitabine 300 mg/m2 i.v. 30 minutes once weekly (10 mg/m2/min). Among unresectable patients, partial response was observed each in one patient, while stable disease was seen in four and five patients (FRI versus SI), respectively. A CBR was achieved in three versus two patients. As side effects, grade 3 toxicities were not observed in patients treated with the FRI regimen. The median survival time was 10 months versus 8 months, and this survival difference is not statistical significant. In the adjuvant setting with GEM, 5 of 7 patients treated with the SI regimen discontinued the treatment within 3 cycles because of severe grade 3 or 4 toxicities in spite of dose reduction, while all patients with FRI regimen achieved the entire treatment. The median survival time and disease-free survival time were no significant difference between two groups. In conclusion, the FRI regimen is well tolerated and offers good palliation, as well as the SI regimen, in patients with locally advanced pancreatic cancer. Furthermore, in the adjuvant setting, the FRI regimen resulted in better clinical benefit on quality of life and fewer side effects than the SI regimen.
Regimen
Cite
Citations (0)
Carboplatin
Cite
Citations (69)
Carboplatin
Mechanism of Action
Cite
Citations (16)
Carboplatin
Regimen
Cite
Citations (25)
Combinations of gemcitabine (Gemzar) with cisplatin (Platinol) are among the most active new chemotherapy regimens developed for advanced non-small-cell lung cancer. Carboplatin (Paraplatin) is a platinum analog devoid of many of the nonhematologic toxicities associated with cisplatin. Although few direct comparisons have been made, when administered by area under the concentration-time curve (AUC) dosing, carboplatin is probably equivalent to cisplatin in advanced non-small-cell lung cancer and provides an improved therapeutic index. Based on its favorable toxicity profile, carboplatin has supplanted cisplatin for use in combination with paclitaxel in several different tumor types. Initial trials combining gemcitabine and carboplatin using standard days 1, 8, and 15 dosing of gemcitabine suggested that thrombocytopenia was problematic. More recently, 21-day schedules in which gemcitabine is administered only on days 1 and 8 have demonstrated both efficacy and improved toxicity profiles. Here we review recent studies investigating gemcitabine plus carboplatin and preliminary data regarding combinations of gemcitabine with the new platinum analog oxaliplatin.
Carboplatin
Cite
Citations (5)
Carboplatin
Cite
Citations (1)
Carboplatin
Regimen
Cite
Citations (15)
Carboplatin
Cite
Citations (4)
To determine if the drug doses and administration schedules of carboplatin and gemcitabine combination affect antitumor effects.The inhibition of cell viability was measured by MTT assay. Median effect analysis was conducted to determine the cytotoxicity activity of carboplatin and gemcitabine combination. Cell cycle changes were analyzed by flow cytometry.Synergism was observed when the bladder cancer cell line 5637 cells were treated with gemcitabine followed by carboplatin or concurrent carboplatin/gemcitabine. In contrast, moderate antagonism was observed when cells were treated with carboplatin followed by gemcitabine. Cell cycle analysis showed that the combined effect of these two drugs was cell cycle disturbance.Different doses and administration schedules affect the antitumor effect of carboplatin/gemcitabine combination that may have clinical significance in the treatment for bladder cancer.
Carboplatin
Cite
Citations (16)
A phase III study of carboplatin vs cisplatin in CAP regimen for ovarian cancer was conducted by a cooperative study group consisting of 22 institutions nationwide. The response rate for 23 cases allocated to carboplatin regimen group was 34.8% and 42.1% for 19 cases allocated to cisplatin regimen group. No significant difference was observed between these two regimens in response rates, and no significant differences were noted between the two regimens in each of the clinical toxicities and abnormalities in laboratory findings. Since the carboplatin regimen group did not require hydration, or the use diuretics or antiemetics, these results suggested that carboplatin is more useful in the treatment of ovarian cancer than cisplatin.
Carboplatin
Regimen
Cite
Citations (10)