Salvage Chemotherapy in Recurrent Platinum-Resistant or Refractory Epithelial Ovarian Cancer with Carboplatin and Distearoylphosphatidylcholine Pegylated Liposomal Doxorubicin (Lipo-Dox<sup>®</sup>)

Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m 2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 44%

Section: Introductionmentioning

confidence: 99%

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Outcomes with Single Agent LIPO-DOX in Platinum-Resistant Ovarian and Fallopian Tube Cancers and Primary Peritoneal Adenocarcinoma - Chiang Mai University Hospital Experience

Suprasert

Manopunya²,

Cheewakriangkrai³

2014

“…In order to reduce side effect of antitumor agents, various drug delivery systems have been developed, such as polymer conjugates, polymeric micelles and liposomes (Torchilin, 2004;Chang et al, 2009;Khemapech et al, 2013;Xu et al, 2013). As an important member of drug delivery systems, polymeric micelles have attracted significant attention in tumor-targeted drug delivery systems recently.…”

Section: Introductionmentioning

confidence: 99%

Isomeric Folate-Conjugated Polymeric Micelles Bind to Folate Receptors and Display Anticancer Effects

Dong¹,

Xie²,

Xie³

et al. 2014

The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through α-or γ-carboxyl groups for antitumor efficacy. The isomeric block copolymers, α-and γ-folate-polyethyleneglycoldistearoyl phosphatidylethanolamine (α-and γ-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and α-/ γ-Fol-PEG-DSPE-DOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the α-/ γ-Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX, α-and γ-Fol-PEG-DSPE-DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both α-and γ-folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between α-and γ-Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through α-or γ-carboxyl groups.

“…Various cytotoxic agents studied e.g. topotecan, PLD, gemcitabine, docetaxel, etoposide, paclitaxel and etc (Karaoglu et al, 2009;Kucukoner et al, 2012;Khemapech et al, 2013;Pitakkarnkul et al, 2013;Su et al, 2013;Yuan et al, 2013;Suprasert et al, 2014) could yield 27% to 65% RR and a median survival of 12-24 months in platinum-sensitive recurrent EOC (Berek et al, 2010). The same list of drugs could have only 10%-30% RR with median survival of only 4-9 months in platinum-resistant diseases.…”

Section: Introductionmentioning

confidence: 99%

Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

Chanpanitkitchot

Tangjitgamol²,

Khunnarong³

et al. 2014

Background: To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent epithelial ovarian cancer (EOC) patients treated with gemcitabine. Materials and Methods: Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. Results: We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinumsensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. Conclusions: Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.