Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study

Rothenberg, Mace L.; Liu, P.Y.; Wilczynski, Sharon P.; Nahhas, William A.; Winakur, Gaye L.; Jiang, Caroline S.; Moinpour, Carol M.; Lyons, Ben; Weiss, Geoffrey R.; Essell, James; Smith, Harriet O.; Markman, Maurie; Alberts, David S.

doi:10.1016/j.ygyno.2004.09.004

Cited by 27 publications

(17 citation statements)

References 25 publications

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“…This low survival rate is because of its frequent diagnosis at an advanced stage and by intrinsic and acquired resistance to platinum-based chemotherapy. In the recurrent disease setting, those patients who experience progression through first-line, platinum-based therapy (platinum refractory), or those who experience relapse within 6 months of receiving platinum therapy (platinum resistant) are typically treated with a second-line non-platinum-based regimen, such as singleagent doxorubicin (7) gemcitabine (8), paclitaxel, topotecan (9), vinorelbine (10), or trabectedin plus pegylated liposomal doxorubicin (11). Agents yielding responses in the range of 15% to 20% that last a median of approximately 4 months, emphasize the great need for novel effective therapeutic strategies for its management (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

Vidal

Muñoz

Guillén

et al. 2012

Clinical Cancer Research

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Purpose: Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecologic malignancies. The low survival rate is because of its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority.Experimental Design: To investigate new treatments in in vivo models reproducing EOCs tumor growth, we generated a preclinical model of ovarian cancer after orthotopic implantation of a primary serous tumor in nude mice. Further, matched model of acquired cisplatin-resistant tumor version was successfully derived in mice. Effectiveness of lurbinectedin (PM01183) treatment, a novel marinederived DNA minor groove covalent binder, was assessed in both preclinical models as a single and a combined-cisplatin agent.Results: Orthotopically perpetuated tumor grafts mimic the histopathological characteristics of primary patients' tumors and they also recapitulate in mice characteristic features of tumor response to cisplatin treatments. We showed that single lurbinectedin or cisplatin-combined therapies were effective in treating cisplatin-sensitive and cisplatin-resistant preclinical ovarian tumor models. Furthermore, the strongest in vivo synergistic effect was observed for combined treatments, especially in cisplatin-resistant tumors. Lurbinectedin tumor growth inhibition was associated with reduced proliferation, increased rate of aberrant mitosis, and subsequent induced apoptosis.Conclusions: Taken together, preclinical orthotopic ovarian tumor grafts are useful tools for drug development, providing hard evidence that lurbinectedin might be a useful therapy in the treatment of EOC by overcoming cisplatin resistance.

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Section: Introductionmentioning

confidence: 99%

Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

Vidal

Muñoz

Guillén

et al. 2012

Clinical Cancer Research

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“…Evidence suggests that platinum-based combination chemotherapy may be superior to singleagent therapy in this situation [6] . Overall response rates reported with several newer cytotoxic agents in ovarian cancer appear similar as follows: topotecan, 20% [7] ; gemcitabine, 19% [8] ; vinorelbine, 20% [9,10] ; liposomal doxorubicin, 26% [11] ; and oral etoposide, 27% in platinum-resistant patients and 35% in platinum-sensitive patients [12] . While the aims of treatment for recurrent or resistant disease traditionally have been palliative, the introduction of pegylated liposomal doxorubicin (PLD) (Caelyx®, Schering-Plough Corporation, Kenilworth, NJ), has demonstrated the ability to increase progression-free survival [13] .…”

Section: Introductionmentioning

confidence: 88%

Pegylated liposomal doxorubicin as a single agent or as combination therapy with carboplatin in patients with recurrent or refractory epithelial ovarian cancer

Shen

Kong

Gao

et al. 2009

Clin. Oncol. Cancer Res.

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OBJECTIVEPegylated liposomal doxorubicin (PLD; CAELYX ® ), a novel formulation of doxorubicin with enhanced therapeutic efficacy and reduced toxicity, has demonstrated improved progression-free survival in recurrent or refractory ovarian cancer. The objective of this open-label, noncomparative, observational study was to determine the effi cacy and safety of PLD monotherapy or combination therapy with carboplatin for patients with recurrent or refractory ovarian cancer. METHODS Sixty-two patients with recurrent or refractory ovarian cancer who completed a platinum-based chemotherapy regimen and demonstrated platinum sensitivity for first-line treatment at least 6 months prior to study entry were enrolled in 20 centers in China. PLD was given as monotherapy (50 mg/m 2 infused over 60 minutes) or as combination therapy (30 mg/m 2 1-hour infusion) with carboplatin (area under the curve 5 mg·min/mL 1-hour infusion) on day 1 every 28 days for 4 cycles. The primary endpoint was objective response (OR) rate or CA-125 level. Secondary endpoints included time to response, time-to-progression, health-related quality of life, and safety. RESULTS Overall, 48% of the 62 evaluable patients achieved a confi rmed OR. More patients receiving PLD and carboplatin achieved an OR vs the PLD monotherapy group (63% vs. 37%). The median time to response and disease progression was 58.5 days and 56.0 days, respectively. Overall and drug-related adverse events were reported for 39% and 34%, respectively. The most commonly reported adverse events were stomatitis (22.6%) and palmar-plantar erythroderma (9.7%). Two deaths were reported. CONCLUSION PLD is an eff ective and well tolerated agent in women with recurrent or refractory epithelial ovarian cancer.

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“…115 For platinum-resistant disease, the preferred agent is a single non-platinum-based agent (i.e., docetaxel, oral etoposide, gemcitabine, liposomal doxorubicin, weekly paclitaxel, topotecan). The activity of the following agents seems to be similar: topotecan, 20% 118 ; gemcitabine, 19% 119,120 ; vinorelbine, 20% 121,122 ; liposomal doxorubicin, 26% 119,120 ; and oral etoposide, 27%. 123 In patients with platinum-resistant disease, the activity for docetaxel is 22%, weekly paclitaxel is 21%, and pemetrexed is 21%.…”

Section: Recurrent Diseasementioning

confidence: 98%

Epithelial Ovarian Cancer

Morgan¹,

Alvarez²,

Armstrong³

et al. 2011

J Natl Compr Canc Netw

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Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study

Cited by 27 publications

References 25 publications

Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

Pegylated liposomal doxorubicin as a single agent or as combination therapy with carboplatin in patients with recurrent or refractory epithelial ovarian cancer

Epithelial Ovarian Cancer

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