Platinum-refractory Ovarian Cancer Research Articles

Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy

Background. Women with ovarian cancer who experience disease progression during or within 6 months of first-line treatment with platinum-based anticancer drugs are considered to have platinum-resistant tumors. These patients have an unfavorable prognosis, and they frequently seek complementary and alternative therapies (CAM). Historically, this represents an understudied and underreported component of ovarian cancer treatment. Case. This report describes the case of a woman with rapidly progressive, platinum-resistant ovarian cancer. Upon initiating self-directed treatment with Haelan951®, a commercially available fermented soy beverage, she entered into a phase of prolonged disease stabilization including improvement in the serum tumor marker CA-125. Conclusion. Fermented soy products are known to contain high concentrations of the isoflavone, genistein, and other compounds that exhibit anticancer activity in preclinical models. This case report supports the prospective evaluation of alternative therapies such as these in patients with platinum-refractory ovarian cancer.

Irinotecan plus mitomycin may be effective in the treatment of women with platinum-refractory ovarian cancer,

Irinotecan plus mitomycin may be effective in the treatment of women with platinum-refractory ovarian cancer,

Combination Chemotherapy With Irinotecan Hydrochloride (CPT-11) and Mitomycin C in Platinum-Refractory Ovarian Cancer

The aim of this study was to examine the level of activity of irinotecan hydrochloride (CPT-11) and mitomycin-C (MMC) combination chemotherapy in a patient population with platinum-refractory ovarian cancer. Patients received CPT-11 (140 mg/m2) in combination with MMC (7 mg/m2) on days 1, 15, 29 until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. Overall, 61 cycles of CPT-11/MMC chemotherapy were delivered to 13 patients. The major toxicity with this regimen was neutropenia, which was brief and reversible. The incidences of grade 3 and 4 neutropenia were 46% (6/13) and 15% (2/13), respectively. The nonhematological toxicities were generally mild and well tolerated. Of the 13 patients, 4 (31%) experienced an objective response (1 CR, 3 PRs). Among responders, the median duration of response was 30 weeks (range, 12 to 292+ weeks). The median time to progression for the 13 patients who received treatment on this trial was 24 weeks (range, 8 to 292+ weeks), with a median survival of 36 weeks (range, 20 to 292+ weeks). This preliminary study shows that the combination of CPT-11 and MMC appears to be an active regimen in patients with refractory ovarian cancer.

Phase 1–2a study of TLK286 (a novel glutathione analog) in combination with carboplatin in platinum refractory or resistant (≥ 3rd line) ovarian cancer

5060 Background: TLK286 (Telcyta) is a novel glutathione analog prodrug activated by GST P1–1, which is overexpressed in ovarian cancer, releasing two electrophilic fragments that induce apoptosis. In vitro, TLK286 is not cross resistant to carboplatin and has shown synergistic inhibition in OVCAR3 cells. TLK286 has demonstrated significant single agent activity in two Phase 2 trials in ovarian cancer. Methods: Platinum refractory or resistant ovarian cancer patients (pts) were treated at doses of 500, 750 or 960 mg/m2 of TLK286 in combination with carboplatin (AUC 5) every 4 weeks until tumor progression or unacceptable toxicity. The objectives were to determine the MTD of the combination, and objective response rate (ORR) by RECIST. Results: At interim analysis, 8 pts median age 56 (range 49–68), prior chemotherapy regimens median 3.5 (range 2–5) have received 44+ cycles (median 4 cycles, range 3–11+). All pts have failed paclitaxel and platinum (platinum resistant 63%, refractory 25%) and additional therapies: Doxil (63%), gemcitabine (25%), topotecan (38%) and others (75%). Most common adverse events (AEs) related to TLK286/carboplatin are Grade 1–2 fatigue (5 pts), nausea (8), vomiting (3), neutropenia (3), leukopenia (7). Grade 3 fatigue, vomiting and leukopenia were reported in 1 pt, thrombocytopenia in 3 pts and neutropenia in 5 pts. No Grade 4 AEs or dose limiting toxicities were observed. One CR (13%), 4 PRs (50%) and 3 SDs (38%) are shown (ORR=63% and DSR=100%). Conclusions: TLK286 at 50% of the single agent dose (500 mg/m2) in combination with carboplatin (AUC 5) shows enhanced efficacy with ORR of 63% and DSR of 100% in platinum refractory or resistant (≥ 3rd line) ovarian cancer pts. Further pt follow-up and dose escalation continues. The TLK286/carboplatin combination is an active regimen for future studies in ovarian, NSCLC and breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Telik, Inc. Telik, Inc. Telik, Inc. Telik, Inc. Telik, Inc.

Phase 1–2a study of TLK286 (a novel glutathione analog) in combination with carboplatin in platinum refractory or resistant (≥ 3rd line) ovarian cancer

5060 Background: TLK286 (Telcyta) is a novel glutathione analog prodrug activated by GST P1–1, which is overexpressed in ovarian cancer, releasing two electrophilic fragments that induce apoptosis. In vitro, TLK286 is not cross resistant to carboplatin and has shown synergistic inhibition in OVCAR3 cells. TLK286 has demonstrated significant single agent activity in two Phase 2 trials in ovarian cancer. Methods: Platinum refractory or resistant ovarian cancer patients (pts) were treated at doses of 500, 750 or 960 mg/m2 of TLK286 in combination with carboplatin (AUC 5) every 4 weeks until tumor progression or unacceptable toxicity. The objectives were to determine the MTD of the combination, and objective response rate (ORR) by RECIST. Results: At interim analysis, 8 pts median age 56 (range 49–68), prior chemotherapy regimens median 3.5 (range 2–5) have received 44+ cycles (median 4 cycles, range 3–11+). All pts have failed paclitaxel and platinum (platinum resistant 63%, refractory 25%) and additional therapies: Doxil (63%), gemcitabine (25%), topotecan (38%) and others (75%). Most common adverse events (AEs) related to TLK286/carboplatin are Grade 1–2 fatigue (5 pts), nausea (8), vomiting (3), neutropenia (3), leukopenia (7). Grade 3 fatigue, vomiting and leukopenia were reported in 1 pt, thrombocytopenia in 3 pts and neutropenia in 5 pts. No Grade 4 AEs or dose limiting toxicities were observed. One CR (13%), 4 PRs (50%) and 3 SDs (38%) are shown (ORR=63% and DSR=100%). Conclusions: TLK286 at 50% of the single agent dose (500 mg/m2) in combination with carboplatin (AUC 5) shows enhanced efficacy with ORR of 63% and DSR of 100% in platinum refractory or resistant (≥ 3rd line) ovarian cancer pts. Further pt follow-up and dose escalation continues. The TLK286/carboplatin combination is an active regimen for future studies in ovarian, NSCLC and breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Telik, Inc. Telik, Inc. Telik, Inc. Telik, Inc. Telik, Inc.

A phase 2, single agent study of CI-1033 administered at two doses in ovarian cancer patients who failed platinum therapy

5054 Background: Ovarian cancer that is refractory to platinum-based therapies is a therapeutic challenge, particularly in the setting of erbB-1 and -2 receptor over- expression. CI-1033 is an irreversible, 4-anilinoquinazoline pan-erbB tyrosine kinase inhibitor with activity in a wide variety of human tumor xenografts, particularly erbB+ tumors including ovarian SK-OV-3. Methods: This study evaluated 50- and 200mg doses of CI-1033, given daily for 21 days repeated every 28 until disease progression in pts with platinum-refractory ovarian cancer. Primary eligibility criteria included disease progression following platinum therapy, measurable disease, and Karnofsky Performance Status (KPS) of 60–100. Baseline tumor erbB receptor profiles were determined by IHC staining retrospectively in 56 of the 105 pts. Endpoints included 1-yr progression-free survival (PFS) and overall survival (OS). Results: Between January and May of 2002, 105 patients were enrolled. Baseline characteristics were balanced between both groups: overall median number of prior chemotherapy regimens was 4 (1–12); median KPS was 90. Fifty-three pts received 146 cycles in the 50-mg arm; 52 pts received 138 cycles in the 200-mg arm. Dose reductions were necessary in 59% of pts in the 200-mg arm predominantly due to gastrointestinal adverse effects (AEs); no pts required dose reductions in the 50-mg arm. The most common treatment-related AEs in the 50-mg arm were Grade 1–2 diarrhea (57%), asthenia (43%), and nausea (41%); AEs in the 200-mg arm were Grade 2–3 diarrhea (85%), stomatitis (69%), and rash (58%). There were no objective responders in either arm; stable disease (≥8 weeks) was achieved in 28% and 34% of pts in the 50- and 200-mg arms, respectively. One-yr PFS rates were 0% and 9%, and 1-year OS were 37% and 38% for 50- and 200-mg dose group, respectively. No associations were apparent between baseline tumor erbB expression profiles and PFS or OS. Conclusions: CI-1033 has minimal activity in this heavily pretreated, platinum-refractory population. The 50-mg dosing regimen was better tolerated than the 200-mg arm, with gastrointestinal AEs being most common toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Employed by Pfizer Eli-Lilly Pfizer Eli Lilly; GlaxoSmithKline

A phase 2, single agent study of CI-1033 administered at two doses in ovarian cancer patients who failed platinum therapy

5054 Background: Ovarian cancer that is refractory to platinum-based therapies is a therapeutic challenge, particularly in the setting of erbB-1 and -2 receptor over- expression. CI-1033 is an irreversible, 4-anilinoquinazoline pan-erbB tyrosine kinase inhibitor with activity in a wide variety of human tumor xenografts, particularly erbB+ tumors including ovarian SK-OV-3. Methods: This study evaluated 50- and 200mg doses of CI-1033, given daily for 21 days repeated every 28 until disease progression in pts with platinum-refractory ovarian cancer. Primary eligibility criteria included disease progression following platinum therapy, measurable disease, and Karnofsky Performance Status (KPS) of 60–100. Baseline tumor erbB receptor profiles were determined by IHC staining retrospectively in 56 of the 105 pts. Endpoints included 1-yr progression-free survival (PFS) and overall survival (OS). Results: Between January and May of 2002, 105 patients were enrolled. Baseline characteristics were balanced between bot...

Phase 1–2a dose ranging study of TLK286 (a novel glutathione analog) in combination with liposomal doxorubicin in platinum refractory or resistant ovarian cancer

Phase 1–2a dose ranging study of TLK286 (a novel glutathione analog) in combination with liposomal doxorubicin in platinum refractory or resistant ovarian cancer

Phase 1–2a dose ranging study of TLK286 (a novel glutathione analog) in combination with liposomal doxorubicin in platinum refractory or resistant ovarian cancer

5062 Background: TLK286 (Telcyta) is a glutathione analog prodrug activated by GST P1–1, which is overexpressed in ovarian cancer. Activation by GST P1–1 releases two electrophilic fragments that i...

TLK 286.

TLK 286 [TELCYTA] is an antitumour agent in clinical development with Telik. It was developed through the application of Telik's proprietary TRAP chemogenomics technology. TLK 286 works by targeting tumours that overexpress glutathione S-transferase (GST) P1-1, an enzyme that has been implicated in drug resistance and poor prognosis, and is elevated in solid tumours such as head and neck, breast, gastrointestinal, lung and ovarian tumours. TLK 286 is activated by GST P1-1 and, subsequently, initiates apoptosis in targeted tumour cells. Telik owns worldwide rights to TLK 286 and intends to commercialise it in the North American market. The company plans to select a collaborator in other territories with capabilities in manufacturing, sales and marketing. Telik was previously collaborating with Taiho, Japan, on development of TLK 286, but this agreement appears to have been terminated. Telik announced in October 2002 that it had begun the first of a series of planned clinical trials of TLK 286 in combination with docetaxel in patients with non-small cell lung cancer. A phase II trial was initiated in May 2001 in patients with ovarian cancer. Two additional combination trials were initated in ovarian cancer patients in December 2002. One of the trials will evaluate the combination of TLK 286 with Doxil in patients who have failed platinum-based chemotherapy. The second trial will evaluate TLK 286 in combination with carboplatin in patients who have recurrent, platinum-sensitive ovarian cancer. Telik held a successful phase III meeting with the US FDA to discuss plans for the first registration trial of TLK 286, and in March 2003 it was announced that a phase III registration trial of TLK 286 as monotherapy had been initiated in platinum-refractory ovarian cancer patients. The multinational trial has been designated the ASSIST-1 (Assessment of Survival in Solid Tumours-1) trial. Telik plans to enrol approximately 440 women who will be assigned to either TLK 286 treatment or a control (doxorubicin liposomal or topotecan).

Docetaxel: an alternative taxane in ovarian cancer.

The taxanes paclitaxel and docetaxel are potent chemotherapeutic agents that block tubulin depolymerisation, leading to the inhibition of microtubule dynamics and cell cycle arrest. Although docetaxel and paclitaxel share a mutual tubulin binding site, mechanistic and pharmacological differences exist between these agents. For example, docetaxel has increased potency and an improved therapeutic index compared with paclitaxel, and its short 1-h infusion offers a substantial clinical advantage over the prolonged infusion durations required with paclitaxel. In clinical studies, docetaxel monotherapy demonstrated good response rates and an acceptable toxicity profile in both paclitaxel- and platinum-refractory ovarian cancer patients. In particular, neurotoxicity — a dominant side effect with both paclitaxel and cisplatin — occurs at a low incidence with docetaxel, making docetaxel a promising agent for combining cisplatin and other platinum compounds. In Phase II studies, the combination of docetaxel with either cisplatin or carboplatin has yielded impressive response rates of 69–74 and 81–87%, respectively. Furthermore, Phase III data suggest that docetaxel–carboplatin and paclitaxel–carboplatin are similarly efficacious with respect to progression-free survival and clinical response, although neurotoxicity occurs more frequently with the paclitaxel regimen. While paclitaxel–carboplatin remains the standard treatment for the management of advanced ovarian cancer, docetaxel–carboplatin appears to be a promising alternative, particularly in terms of minimising the incidence and severity of peripheral neuropathy.

ATP chemosensitivity testing in ovarian and breast cancer: early clinical trials.

After disappointing results achieved with older chemosensitivity tests such as the human tumor clonogenic assay (HTCA) during the 1980s, the last decade has seen a renaissance of the concept of individualized chemotherapy in oncology, markedly stimulated by the development of newer nonclonogenic assays. These methods appear to be able to overcome major technical limitations associated with older assays, now allowing for successful testing of most of the tumor specimens submitted. Currently, the ATP-based tumor chemosensitivity assay (ATP-TCA) can be regarded as the most sophisticated assay to investigate both solid samples and effusions derived from patients with various organ tumors. During the last 5 years, the ATP-TCA has been used successfully to screen for novel drug combinations for further clinical use in both ovarian and breast cancer such as mitoxantrone plus paclitaxel (NT) and treosulfan plus gemcitabine (TG), respectively. Clinical trials that have been set up in heavily pretreated patients with recurrent ovarian or breast cancer have convincingly confirmed the high activity of these combinations previously demonstrated in preclinical investigations using the ATP-TCA. In a recent phase II trial performed in 59 patients with relapsed ovarian carcinoma, ATP-TCA-directed therapy was able to triple the response rate and to double the survival time, compared with published empirical chemotherapy regimes. Preliminary results with ATP-TCA-directed therapy in breast cancer also evidenced promising response rates. These results have been confirmed by additional prospective clinical trials using other types of modern nonclonogenic assays. A phase III trial that is now actively recruiting patients with platinum-refractory ovarian cancer to verify the promising phase II studies will prove the further value of the ATP-TCA as a predictor applicable in routine clinical oncology.

No rules without exception: a long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer

No rules without exception: a long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer

No rules without exception: long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer.

Second-line chemotherapy in platinum/paclitaxel-resistant ovarian cancer induces an objective response in <15% and third-line chemotherapy results in responses less than 10%. Chemotherapy always results in side effects with the risk of a low quality of life. Endocrine therapy is used world-wide among chemo-resistant ovarian cancer. Tamoxifen is a standard palliative treatment in many centers. LH-RH (luteinizing hormone-releasing hormone) agonists have also demonstrated activity among patients with ovarian cancer in several studies with response rates of 9-12% and disease stabilization in 15-26% of these women. In this retrospective study 32 patients with ovarian cancer who had relapsed after platinum/paclitaxel-based first-line chemotherapy and had exhausted all standard treatments received LH-RH analogue Leuprorelin depot 3.75 mg sc once a month until tumor progression. One patient (3%) had a complete response, with remission time over 3 years. Two patients (6%) reached partial response with remission time of 3 and 4 months. Four patients (12%) remained stable for a mean time of 7 months (range 4-12 months). The remaining 25 patients (78%) had progressive disease. The treatment was well tolerated, and no major toxicity has been reported. This study showed that LH-RH agonist Leuprorelin has only a limited effect in patients pretreated with platinum-based chemotherapy.

Polyethylene Glycol-Liposomal Doxorubicin

Polyethylene glycol (PEG)-liposomal doxorubicin is a formulation of the anthracycline doxorubicin in which the drug is encapsulated in PEG-coated liposomes. This alters the pharmacokinetic properties of doxorubicin, prolonging circulation time and enhancing localisation to tumours. In a large randomised trial, intravenous PEG-liposomal doxorubicin was at least as effective as topotecan in patients with ovarian cancer refractory or sensitive to first-line platinum-based chemotherapy. Overall response rates of patients with ovarian cancer refractory to platinum- and paclitaxel-based chemotherapy who received the drug ranged from 18.3 to 27.6% in noncomparative clinical trials. PEG-liposomal doxorubicin also has antitumour activity in patients with metastatic breast cancer pretreated with other chemotherapeutic agents. Overall response rates were similar in patients with pretreated metastatic breast cancer who had received PEG-liposomal doxorubicin or two comparator salvage chemotherapy regimens (vinorelbine or mitomycin C plus vinblastine) in an interim analysis of a large randomised study. In patients with advanced AIDS-related Kaposi's sarcoma, PEG-liposomal doxorubicin monotherapy produced overall response rates ranging from 46 to 77% in randomised trials. The drug was significantly more effective than bleomycin plus vincristine alone or in combination with standard doxorubicin, as measured by tumour response. As a replacement for standard doxorubicin in commonly used combination therapies, PEG-liposomal doxorubicin has shown activity in multiple myeloma and aggressive non-Hodgkin's lymphoma in small, preliminary trials. The most common adverse events associated with PEG-liposomal doxorubicin are myelosuppression, palmar-plantar erythrodysaesthesia, stomatitis and nausea. These can be managed by delaying or reducing dosages. Although preliminary trials are promising, the relative cardiotoxicity of PEG-liposomal doxorubicin compared with the standard formulation has not been clearly established. Monotherapy with PEG-liposomal doxorubicin is effective as a second-line chemotherapy in patients with platinum-refractory ovarian cancer and in patients with metastatic breast cancer. However, as with all chemotherapeutic agents, the benefits of treatment need to be weighed against the agent's tolerability profile. Strong comparative data have helped to establish PEG-liposomal doxorubicin as the first-line treatment option in patients with advanced Kaposi's sarcoma. Anticancer activity has also been observed in studies conducted in small numbers of patients with multiple myeloma or non-Hodgkin's lymphoma receiving PEG-liposomal doxorubicin instead of standard doxorubicin in combination regimens, although further data are needed to confirm the clinical relevance of these findings.

Treatment of advanced ovarian cancer

Chemotherapy for advanced ovarian cancer has evolved over the past 25 years from the initial use of alkylating agents such as melphalan. Combinations containing cisplatin, cyclophosphamide and doxorubicin were studied in the 1980s and showed improved median progression-free survival. The comparison of platinum-based combinations containing alkylating agents (mainly cyclophosphamide) with triple drug combinations containing anthracyclines and alkylating agents did not convincingly show superiority for the more toxic triple drug combinations. Subsequently, cisplatin plus cyclophosphamide was accepted as a new standard treatment. Carboplatin was introduced as an alternative to cisplatin in the early 1990s resulting in a reduced toxicity but similar efficacy. Taxanes were incorporated into the first-line treatment combinations in the mid-1990s, resulting in superior responses and a prolonged survival especially in patients with bulky disease. Despite this, over 50% of all these patients relapse and ultimately die of their disease. Currently, there is no worldwide accepted standard treatment for patients with platinum-refractory ovarian cancer. Topotecan, etoposide, gemcitabine and liposomal doxorubicin have been studied in this patient group and responses of up to 20% can be expected. However, response duration rarely exceeds 12 months and increased efforts are needed in this area of chemotherapy.

Caelyx®: phase II studies in ovarian cancer

While there have been significant advances in first-line chemotherapy for advanced ovarian cancer, most patients still relapse with drug-resistant disease. For patients refractory to the two most active agents (platinum and paclitaxel), there are few salvage regimens that possess significant clinical activity together with minimal treatment-related toxicities. Caelyx® is a new treatment for advanced ovarian cancer, which delivers doxorubicin encapsulated in long-circulating Stealth® liposomes, resulting in a prolonged circulation and enhanced tumour targeting of the drug, together with a markedly different safety profile compared with native doxorubicin. Recent phase II clinical trials in relapsed ovarian cancer have demonstrated efficacy in patients with platinum-refractory disease (defined as progression on or relapse within 6 months of previous therapy). In those with combined platinum/paclitaxel-refractory disease, the response rate was 14.5% (95% Confidence Interval (CI): 7.8–21.4%), with many patients demonstrating a prolonged duration of response of beyond 6 months. The most frequent severe (grade 3/4) toxicity with Caelyx® was palmar-plantar erythrodysesthesia (PPE), which occurred in 25% of patients and was managed by dose modification or lengthening the treatment cycle. The incidence of neutropenia and alopecia was much reduced, and the cardiac safety profile was also improved compared with equivalent cumulative anthracycline doses for native doxorubicin. In summary, the evidence of clinical efficacy in patients with platinum-refractory ovarian cancer together with an improved safety profile are all strongly supportive of a positive benefit-risk profile for Caelyx® in the treatment of advanced ovarian cancer following failure of first-line platinum-based therapy

The Costs and Efficacy of Liposomal Doxorubicin in Platinum-Refractory Ovarian Cancer in Heavily Pretreated Patients

Objective. In clinical practice, chemotherapy agents demonstrating modest second-line activity against platinum-refractory epithelial ovarian cancer (PROC) are frequently used in patients who have received multiple prior chemotherapy agents. Whether the response rates reported in selected patients can be expected in heavily pretreated patients is not known. Similarly, the costs of palliative chemotherapy are not known. We sought to determine the response, survival, and predictors of response in an unselected cohort of PROC patients receiving liposomal doxorubicin (LD) for relapsed disease, and the overall costs of delivering liposomal doxorubicin in this setting.Methods. In a cohort of 62 consecutive patients who initiated LD as second- or greater-line therapy for PROC, the following variables were examined: age, number of prior regimens for relapse disease, duration of first clinical remission, time from last prior treatment, dose intensity of LD received, response/clinical benefit, time to progression, toxic effects, and survival. Multivariate analyses were used to identify predictors of clinical benefit and overall survival. Direct medical charges were calculated and converted to costs, and major cost drivers determined.Results. Sixty-two patients received a total of 174 cycles of LD. The mean number of cycles per patient was 2 (range, 1–8); the median number of prior regimens for recurrent PROC was 2 (range, 0–8); and the median duration of the first clinical remission was 6 months. Median dose intensity of LD delivered was 11.4 mg/m2/week (range, 2.8–16.7 mg/m2/week). Nine of sixty-two patients (14.5%) had an objective clinical response by CA-125 and/or CT scan (95% confidence interval, 6–23%). Grade 3/4 toxicity occurred in 11% of patients. In the full cohort, median time to progression was 2.2 months, and median overall survival, 9.6 months (range, 0.2–26 months). Dose intensity was the only independent predictor of overall response. Duration of first clinical remission and number of prior salvage regimens were associated with longer overall survival. The mean total direct medical cost per cycle of LD was $5763, and the major cost drivers were hospitalizations and drug acquisition/delivery costs.Conclusion. LD is an active agent in PROC, even when used as greater-than-second-line therapy. Among heavily pretreated patients, delivering a dose intensity of at least 9.0 mg/m2/week was associated with a higher probability of response. The cost per cycle of LD is driven by hospitalizations and drug acquisition/delivery costs.

PCN11: ECONOMIC EVALUATION OF LIPOSOMAL DOXORUBICIN VS TOPOTECAN FOR RECURRENT OVARIAN CANCER IN THE UK

OBJECTIVES: To conduct an economic evaluation of an open label, phase III randomized trial involving centers in North America and Europe. METHODS: There were 239 and 235 patients in the liposomal doxorubicin (50mg/m2 every 4 weeks) and topotecan (1.5mg/m2 for 5 days every 3 weeks) arms, respectively. Overall median survival was 420 days and 397 days for liposomal doxorubicin and topotecan, respectively (hazard ratio = 1.12 (90% CI 0.92,1.37; p = .34)). Because the outcomes were not clinically different for the 2 groups, a cost minimization analysis was performed. Costs included were: study drug; drug administration; and management of adverse events. Actual mg of drug administered and frequency and severity of adverse events were obtained from the clinical trial. Expert opinion was used to estimate the resources used in the treating adverse events, and unit costs were based on UK practice data. Further validation of the expert opinion is currently underway. RESULTS: Severe (Grade III/IV) toxicities were more frequent for liposomal doxorubicin versus topotecan in terms of palmar-plantar erythrodysesthesia (PPE) (n = 64 vs. 0), and stomatitis/pharyngitis (n = 32 vs. 2) but less frequent for thrombocytopenia (n = 3 vs. 238), anemia (n = 19 vs. 146), neutropenia (n = 55 vs. 764) and fever (n = 2 vs. 13). The average cost per patient was estimated to be EUR16,230 (95% CI 14,780 to 17,680) and EUR20,554 (95% CI 18,764 to 22,344) for liposomal doxorubicin and topotecan, respectively. Per patient cost for drug + administration were similar between the two groups, (EUR14,974 and EUR15,073); the main differential in cost was management of anemia (EUR407 and EUR2,219) and neutropenia (EUR57 and EUR1,454) for the liposomal doxorubicin and topotecan groups, respectively. CONCLUSIONS: In settings where the current standard of care for platinum refractory or resistant ovarian cancer is topotecan, liposomal doxorubicin offers the potential for savings through reduction in cost of adverse event management.

New drugs in gynecologic cancer.

The implementation of new drug treatments has improved the prognosis for advanced cancers of the cervix, uterus, and ovary. Platinum analogs are the most effective drugs in the treatment of ovarian cancer. Other drugs, such as oxaliplatin, have been proposed as a rational treatment of platinum refractory ovarian cancer. Epothilones are also being studied in clinical trials, as are histone deacetylase inhibitors. Several promising agents may soon receive Food and Drug Administration approval.