Carboplatin Plus Paclitaxel Versus Carboplatin Plus Pegylated Liposomal Doxorubicin As First-Line Treatment for Patients With Ovarian Cancer: The MITO-2 Randomized Phase III Trial

Pignata, Sandro; Scambia, Giovanni; Ferrandina, Gabriella; Savarese, Antonella; Sorio, Roberto; Breda, Enrico; Gebbia, Vittorio; Musso, Pietro; Frigerio, Luigi; Medico, Pietro Del; Lombardi, Alessandra; Febbraro, Antonio; Scollo, Paolo; Ferro, Antonella; Tamberi, Stefano; Brandes, Alba A.; Ravaioli, Alberto; Valerio, Maria Rosaria; Aitini, Enrico; Natale, D.; Scaltriti, Laura; Greggi, Stefano; Pisano, Carmela; Lorusso, Domenica; Salutari, Vanda; Legge, Francesco; Maïo, Massimo Di; Morabito, Alessandro; Gallo, Ciro; Perrone, Francesco

doi:10.1200/jco.2010.33.8566

Cited by 177 publications

(123 citation statements)

References 22 publications

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“…In addition, it was suggested that PLD had a more favorable toxicity profile than CϩP [7], but these findings were not always corroborated in other clinical trials [9,11]. There is a need to clarify the efficacy and toxicity profiles of CϩPLD compared with CϩP in order to facilitate therapeutic decision making and optimize patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…The lower rates of allergic reactions in the CϩPLD regimen suggest that there may be an unknown mechanism by which PLD decreases carboplatin hypersensitivity. This could be of high clinical importance because allergic reac- [19], MITO-2 [9], Hellenic [10].…”

Section: C؉pldmentioning

confidence: 99%

“…Using the Response Evaluation Criteria in Solid Tumors, objective response rates were typically less than 30% for the monotherapies evaluated. These low response rates, coupled with the results of our analysis, suggest that these single-agent treatments generallyhavelowefficacyinthissetting.Recently,therehavebeentrials evaluating the efficacy of novel treatment combinations such a trabectedin with PLD and canfosfamide with PLD compared with single-agent PLD in recurrent or platinum-resistant ovarian cancer [9,10]. In addition, a novel targeted agent, olaparib (a poly[ADP-ribose] polymerase inhibitor), was compared with single-agent PLD in BRCA1-or BRCA2-positive recurrent ovarian cancer patients [35].…”

Section: Single-agent Pldmentioning

confidence: 99%

“…CALYPSO [18] and MITO-2 [9] were phase III trials, whereas Hellenic [10] was a phase II trial. Overall, a total of 970 patients were treated with CϩPLD, and 1,015 patients were treated with CϩP.…”

Section: Study Characteristicsmentioning

confidence: 99%

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The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

et al. 2013

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Background. Recent studies suggest that carboplatin with pegylated liposomal doxorubicin (CϩPLD) is as efficacious as carboplatin with paclitaxel (CϩP) and possibly is more tolerable for ovarian cancer therapy. Pegylated liposomal doxorubicin(PLD)mayalsobeefficaciousandtolerableasmonotherapyin recurrent or platinum-resistant disease. We performed a metaanalysis of randomized trials in order to elucidate the role of PLD in ovarian cancer. Methods. We searched PubMed, Scopus, and ISI Web of Knowledge for studies comparing CϩPLD with CϩP and comparing PLD with another monotherapy. Summary hazard ratios (HRs) and relative risks with their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effects model. Results. Three trials were included in the doublet regimen analysis, and five trials were included in the monotherapy regimen analysis. CϩPLD provided superior progression-free survival (PFS) (HR, 0.87; 95% CI, 0.78 -0.96) and similar overall survival (OS; HR, 0.95; 95% CI, 0.84 -1.07) compared with CϩP. There was no evidence of improved tolerability: CϩPLD had more gastrointestinal toxicity, anemia, thrombocytopenia, cutaneous toxicity, and mucositis/stomatitis, although there was less neutropenia, neuropathy, and alopecia. PLD monotherapy had similar PFS (HR, 0.99; 95% CI, 0.89 -1.11) and OS (HR, 0.99; 95% CI, 0.88 -1.11) to other monotherapies, but it was more tolerable. There was less neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity, although cutaneous toxicity was increased. Conclusion. CϩPLD had better PFS and similar OS compared with CϩP and had a very different toxicity profile. Therapy selection could be based on patient risks for side effects. PLD is as efficacious as other monotherapies and is more tolerable. The Oncologist 2013;18:1022-1031 Implications for Practice: Carboplatin with paclitaxel (CϩP) has been the standard first-line chemotherapy regimen for ovarian cancer patients; however, two large randomized trials of carboplatin and pegylated liposomal doxorubicin (CϩPLD) versus CϩP suggest that CϩPLD is as efficacious as CϩP and possibly is more tolerable. The results of our analysis showed that CϩPLD has better progression-free survival than CϩP and similar overall survival; however, we did not find CϩPLD to be more tolerable than CϩP. The toxicity profiles were very different, and therapy selection could reasonably be based on individual patient risks of side effects. Pegylated liposomal doxorubicin (PLD) is also a treatment option for recurrent or platinum-resistant ovarian cancer, but there is no clear distinction among any of the monotherapy options in this setting. The results of our analysis showed that PLD is as efficacious as other monotherapies and is more tolerable. Consequently, it may be the preferred agent in the palliative setting. INTRODUCTIONOvarian cancer is the leading cause of death from gynecologic malignancies in the United States [1]. Standard first-line treatment includes surgical debulking and platinum-based chemotherapy, us...

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Section: Introductionmentioning

confidence: 99%

Section: C؉pldmentioning

confidence: 99%

Section: Single-agent Pldmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

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The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

et al. 2013

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“…The standard treatment of patients with advanced ovarian cancer is cytoreductive surgery followed by combination chemotherapy with taxanes or doxorubicin and platinating agents (21,22). We also evaluated whether the combination of lipoplatin with doxorubicin ( Table 1).…”

Section: Lipoplatin Synergized With Doxorubicin and Abraxanementioning

confidence: 99%

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Casagrande

Celegato

Borghese

et al. 2014

Clinical Cancer Research

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Purpose: Cisplatin and its platinum derivatives are first-line chemotherapeutic agents in the treatment of ovarian cancer; however, treatment is associated with tumor resistance and significant toxicity. Here we investigated the antitumoral activity of lipoplatin, one of the most promising liposomal platinum drug formulations under clinical investigation.Experimental Design: In vitro effects of lipoplatin were tested on a panel of ovarian cancer cell lines, sensitive and resistant to cisplatin, using both two-dimensional (2D) and 3D cell models. We evaluated in vivo the lipoplatin anticancer activity using tumor xenografts.Results: Lipoplatin exhibited a potent antitumoral activity in all ovarian cancer cell lines tested, induced apoptosis, and activated caspase-9, -8, and -3, downregulating Bcl-2 and upregulating Bax. Lipoplatin inhibited thioredoxin reductase enzymatic activity and increased reactive oxygen species accumulation and reduced EGF receptor (EGFR) expression and inhibited cell invasion. Lipoplatin demonstrated a synergistic effect when used in combination with doxorubicin, widely used in relapsed ovarian cancer treatment, and with the albumin-bound paclitaxel, Abraxane. Lipoplatin decreased both ALDH and CD133 expression, markers of ovarian cancer stem cells. Multicellular aggregates/spheroids are present in ascites of patients and most contribute to the spreading to secondary sites. Lipoplatin decreased spheroids growth, vitality, and cell migration out of preformed spheroids. Finally, lipoplatin inhibited more than 90% tumor xenograft growth with minimal systemic toxicity, and after the treatment suspension, no tumor progression was observed.

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Management of Ovarian Cancer

Konstantinopoulos

Awtrey²

2012

JAMA

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Carboplatin Plus Paclitaxel Versus Carboplatin Plus Pegylated Liposomal Doxorubicin As First-Line Treatment for Patients With Ovarian Cancer: The MITO-2 Randomized Phase III Trial

Abstract: Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.

Cited by 177 publications

References 22 publications

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Management of Ovarian Cancer

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