Platinum retreatment of platinum-resistant ovarian cancer after nonplatinum therapy.
ABSTRACT The objective was to determine the response rate to platinum retreatment of "platinum-resistant" ovarian cancer after intervening nonplatinum therapy.
We retrospectively identified 30 patients with platinum-resistant ovarian cancer who received nonplatinum chemotherapy for recurrent epithelial ovarian cancer prior to additional platinum therapy. All patients were treated between July 1, 1997, and June 30, 2001. Platinum resistance was defined as less than a partial response to platinum therapy or progression within 6 months of the last platinum therapy.
Overall, 7 of 30 patients experienced an objective response to platinum therapy (partial response, 23%; complete response, 0%) based on CT scan (2/21) and/or CA-125 (5/9) criteria. The median time to progression for the group was 17 weeks (range, 4-59 weeks). Several predictive factors were identified. The interval since the last platinum treatment did not appear to be predictive in this group. Only 1 of 16 patients who did not have an objective response to the most recent platinum-based therapy responded to platinum rechallenge. Similarly, no patient who received more than three intervening nonplatinum treatments responded to additional platinum therapy (0/10).
Our small retrospective series suggest that the platinum-resistant category is heterogenous and includes patients who may respond to retreatment with platinum-based agents. This group includes the patients with prior platinum responses and early progression. However, patients without an objective response to the last prior platinum therapy or more than three intervening treatments are unlikely to respond to subsequent platinum therapy.
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ABSTRACT: Purpose Preclinical data showed that trientine, a copper-lowering agent, re-sensitized cancer cells to carboplatin through enhanced human copper transporter 1 (hCtr1) -mediated platinum uptake. Experimental Design We studied carboplatin and trientine in patients (n = 55; 45 who had failed platinum) with advanced malignancies (Phase I, modified 3 + 3 design). Results The most common cancers were head and neck (n = 13), non-small cell lung (n = 10) and epithelial ovarian (n = 8). The median number of prior regimens was four. No dose-limiting toxicity or treatment-related deaths were observed at doses up to carboplatin AUC 6 given with trientine. Eight patients achieved stable disease (SD) ≥ 6 months (six platinum failures) and one patient with platinum-resistant ovarian cancer, partial response (PR) (total SD ≥ 6 months/PR = 9, 16.4 %). The mean nadir serum copper level in the nine patients with SD ≥ 6 months/PR was 0.55 μg/mL (95 % CI, 0.34-0.75) versus 1.22 μg/mL (95 % CI, 1.02-1.42) (p < 0.001) in 38 tested patients with progression. In patients who maintained their ceruloplasmin (major copper-carrying protein) levels at 5-15 mg/dL (n = 9), the median progression-free and overall survivals were 9.2 and 15.2 months versus 1.9 (p = 0.001) and 5.7 months (p = 0.033) in patients who did not (n = 38), respectively. Conclusions The combination of a copper-lowering agent with carboplatin was well tolerated and associated with antitumor activity, especially in patients in whom copper and/or ceruloplasmin levels were lowered. Further investigation of this strategy for reversing platinum resistance is warranted.Investigational New Drugs 12/2013; · 3.50 Impact Factor
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ABSTRACT: Objective: Oncologists usually avoid retreatment with drugs to which patients have shown secondary resistance or a mixed response. Here, we report our findings in a pilot study in patients rechallenged with agents previously producing prolonged stable disease (SD), partial or complete remission (PR/CR) or a mixed response, followed by progression. Results: Eleven individuals with advanced cancers (median number of prior systemic therapies in the metastatic setting = 4, range 2-7) were included (8 men; median age 57 years; median Eastern Cooperative Oncology Group performance status of 1). The median duration between initial treatment and retreatment was 92 weeks. Eight of 11 patients (73%) on a retreatment regimen showed SD ≥24 weeks/PR/CR. Of these 8 individuals, 2 were retreated with the same agent(s), 1 with a different agent possessing the same mechanism of action (e.g., in case of an epidermal growth factor receptor inhibitor, using gefitinib first, then erlotinib), and 5 with the same agent(s) in combination with other agents. Conclusion: Our pilot data suggest that patients who develop acquired resistance after durable SD/CR/PR or who have an initial mixed response may attain SD ≥6 months/PR/CR with a retreatment approach. © 2013 S. Karger AG, Basel.Oncology 12/2013; 85(6):350-355. · 2.17 Impact Factor