A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study

OBJECTIVES: Docetaxel is an inhibitor of microtubule depolymerization and has demonstrated activity in paclitaxel-resistant breast cancer and gynecologic cancer. The Gynecologic Oncology Group (GOG) conducted a study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma to determine its activity, and nature and degree of toxicity, in this cohort of patients. METHODS: Patients with platinum- and paclitaxel-resistant ovarian or peritoneal carcinoma, defined as progression while on or within 6 months of therapy, were eligible if they had measurable disease and had not received more than one chemotherapy regimen. Docetaxel at a dose of 100 mg/m(2) was administered iv over 1 h every 21 days. A prophylactic regimen of oral dexamethasone 8 mg bid was begun 24 h before docetaxel administration and continued for 48 h thereafter. Hepatic function was strictly monitored. RESULTS: Sixty patients were entered and treated with a total of 256 courses, with all 60 evaluable for toxicity and 58 evaluable for response. Responses were observed in 22.4% of patients, with 5.2% achieving complete response and 17.2% achieving partial response (95% CI, 12.5-35.3%). The median duration of response was 2.5 months. The likelihood of observing a response did not appear to be related to the length of the prior paclitaxel-free interval or duration of prior paclitaxel infusions. The principal adverse effect of grade 4 neutropenia occurred in 75% of patients. There was one treatment-related death. Dose reductions were required in 36% of patients. CONCLUSIONS: Docetaxel is active in paclitaxel-resistant ovarian and peritoneal cancer but, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule.     

Evaluation of pegylated liposomal doxorubicin (Doxil) as second-line chemotherapy of squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group

OBJECTIVE: Doxorubicin has reported activity in advanced and recurrent cervical cancer but hematologic toxicity has limited its use in some combinations. To determine the level of activity and potential for use in future combinations, a phase II trial of pegylated liposomal doxorubicin as second-line therapy in advanced and recurrent cervical cancer was performed. METHODS: Eligible patients had squamous cell carcinoma of the cervix, measurable disease, one prior chemotherapy regimen which did not include an anthracycline, absolute neutrophil count (ANC) > 1500/microl, platelet count > 100,000/microl, and adequate hepatic function. Pegylated liposomal doxorubicin 40 mg/m(2) was administered intravenously over 1 h every 4 weeks. RESULTS: Twenty-seven patients were entered on this study. All patients were evaluable for toxicity and 26 were evaluable for response. A median of 2 courses of therapy (range 1-10) was given. No grade 4 toxicities were noted. Three patients (11.1%) had partial responses. CONCLUSION: Liposomal doxorubicin has limited activity, at the dose and schedule employed in previously-treated cervical cancer.     

A phase I trial of gemcitabine and topotecan in previously treated ovarian or peritoneal cancer: a Gynecologic Oncology Group study

OBJECTIVE: To determine the maximum tolerated dose (MTD) of the combination of gemcitabine and topotecan in women with previously treated epithelial ovarian, peritoneal, or fallopian tube cancer. METHODS: Patients with recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. Initial treatment was gemcitabine at a dose of 800 mg/m(2) on days 1, 8, and 15 and topotecan at a dose of 0.5 mg/m(2) on days 2-5, with cycles repeated every 28 days. Dose escalations were planned first for topotecan (Cohort I, Dose Levels 1-5) then for gemcitabine (Cohort II, Dose Levels 6-9) until the MTD was reached. RESULTS: Ten patients received a total of 29 cycles. When none of the first four patients could complete therapy as prescribed due to toxicity, doses for each drug were reduced by 1 day. The next six patients were treated at the modified schedule of gemcitabine days 1 and 8 and topotecan days 2-4 (Dose Level -1). Despite this modification, dose-limiting toxicities including neutropenia, thrombocytopenia, and stomatitis occurred at Dose Level -1, and the study was closed early. CONCLUSIONS: At both the initial dose schedule and an attenuated schedule, the combination of gemcitabine and topotecan produced dose-limiting toxicities in women with previously treated epithelial ovarian or peritoneal cancer.     

A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Background

Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer.

Methods

Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000 mg/m² daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design.

Results

Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1-10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage.

Conclusions

The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.     

Sequential prolonged oral topotecan and prolonged oral etoposide as second-line therapy in ovarian or peritoneal carcinoma: a phase I Gynecologic Oncology Group study

OBJECTIVE: Preclinical models suggest synergy when topoisomerase I and II inhibitors are given sequentially, but not simultaneously. A phase I study was conducted in previously treated ovarian or peritoneal carcinoma to determine the tolerability (maximum number of days) of sequential oral topotecan and oral etoposide. METHODS: Topotecan (0.8 mg/m(2)) was administered daily (days 1-5) followed by etoposide (50 mg/m(2)) administered daily for up to 5 days (days 8-12). Patients on dose levels 3 and 4 repeated topotecan for up to 5 days starting on day 15 after the initial topotecan and etoposide sequence. Cycles were repeated every 28 days. Dose-limiting toxicities (DLT) were defined as: neutrophils <1000/microl or platelets <50,000/microl before completing administration of etoposide or topotecan; neutropenic fever; platelets <20,000/microl; or a delay greater than 2 weeks in starting cycle 2 due to hematologic toxicity (ANC <1500/microl or platelets <100,000/microl on scheduled day of treatment). RESULTS: Nineteen patients were entered into this trial, and a total of 54 cycles (range 1-10) of therapy were administered. Dose-limiting toxicities, principally neutropenia, occurred when therapy was administered for 3 of 4 weeks. CONCLUSION: Oral topotecan and oral etoposide administered at these doses daily for 5 days sequentially for a maximum of three (out of every four) weeks of therapy are tolerable. In some cases, it may be necessary to hold therapy the third week. Based on the activity seen in this patient population, it is planned to take this regimen into a phase II setting.     

A phase I study with an expanded cohort to assess the feasibility of intraperitoneal carboplatin and intravenous paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: A Gynecologic Oncology Group study

Objective

This study aimed to determine the first-cycle maximum tolerated dose (MTD) of intraperitoneal carboplatin in combination with intravenous paclitaxel and then assess the feasibility of this dose over multiple cycles.

Methods

Beginning at an intraperitoneal (IP) carboplatin dose area under the curve (AUC) of 5 and a fixed intravenous dose of 175 mg/m² paclitaxel, patients were entered on a dose-escalating phase evaluating first-cycle dose-limiting toxicity (DLT). After estimating the MTD, cohorts of 20 patients were then entered in an expanded phase to evaluate DLT over four cycles.

Results

Twenty-one patients were entered on the dose-escalating phase. A first-cycle MTD of carboplatin at AUC 8 was tolerated although thrombocytopenia was dose-limiting over multiple cycles. An additional 69 patients were treated in expanded cohorts. Only 5/90 (5.6%) patients discontinued treatment because of a port problem. Four-cycle DLT required de-escalation to a carboplatin AUC of 6, and even at that dose, there were 14 dose-limiting toxic effects in 40 patients (35%). Seven dose-limiting toxicities were due to neutropenia, and 6 were due to grade 3/4 thrombocytopenia. Six cycles of therapy were completed in 75% of eligible patients, but dose adjustments were required.

Conclusions

The first-cycle MTD did not predict the tolerability of this regimen over multiple cycles. Using an IP carboplatin dose of AUC 6 in combination with paclitaxel, the regimen can be administered with a high completion rate over multiple cycles. Because neutropenia is a frequent DLT, the addition of hematopoietic growth factors may permit a high completion rate while maintaining this dose.     

脂质体多柔比星联合卡铂治疗复发性卵巢上皮性癌的临床研究

目的 评价脂质体多柔比星+卡铂方案治疗复发性卵巢上皮性癌(卵巢癌)的疗效和副反应.方法 2003年7月-2007年12月间北京肿瘤医院妇瘤科共收治67例卵巢癌(包括原发性腹膜腺癌8例,因其生物学行为和治疗同卵巢癌,故列入本研究)患者,所有患者初次治疗均接受了肿瘤细胞减灭术及以铂类为基础的联合化疗,复发后使用脂质体多柔比星(35～40 ms/m2)+卡铂(血浆浓度时间曲线下面积=5,每4周为1个疗程)作为一线或二线及以上化疗方案治疗,观察其有效率和生存率,并且评估其化疗副反应的发生率.结果 67例患者中,49例患者可进行疗效评估,其中完全缓解23例(47%),部分缓解13例(27%),病情平稳3例(6%),疾病进展10例(20%),有效(完全缓解+部分缓解)率为73%;中位疾病无进展生存时间为8个月;1年和2年生存率分别为73%和55%.67例患者中,2例因过敏样输液反应终止治疗;4例出现胸闷为主要症状的急性输液反应(因停药后再次使用时无任何不良反应发生,所以未终止治疗);2级和3级手足综合征分别为2例(3%)和3例(4%);2例(3%)患者出现4级121腔炎;3级白细胞减少8例(12%).无一例发生4级白细胞减少或与药物相关的心脏毒性反应.结论 脂质体多柔比星+卡铂方案治疗复发性卵巢癌具有一定的疗效,患者对治疗的耐受性良好,可作为治疗复发性卵巢癌的选择之一.     

Phase I feasibility trial of carboplatin, paclitaxel, and gemcitabine in patients with previously untreated epithelial ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study

PURPOSE: To determine the feasibility of administering a minimum of four cycles of carboplatin, paclitaxel, and gemcitabine (CPG) every 21 days without excessive dose modification or cycle delay in patients with previously untreated epithelial ovarian cancer or primary peritoneal cancer. METHODS: Paclitaxel 175 mg/m(2) was given over 3 h followed by carboplatin concentration time curve (AUC) 5 (day 1) and gemcitabine 1 g/m(2) (days 1 and 8) in the first cohort. A second cohort received paclitaxel 135 mg/m(2) over 3 h followed by carboplatin AUC 5 (day 1) and gemcitabine 800 mg/m(2) (days 1 and 8). A maximum of eight cycles was administered. RESULTS: Fourteen patients received 89 cycles during the first cohort. Seven patients experienced 19 hematologic dose-limiting events (DLEs) within the first four cycles, including grade 4 thrombocytopenia (n = 9), febrile neutropenia (n = 3), and omission of gemcitabine on day 8 (n = 7). This exceeded the threshold for nonfeasibility. In the second, less intense regimen, 36 patients were entered. Thirty-one evaluable patients received a total of 200 and median of 6 (range: 2-8) cycles. Thirteen of the thirty-one had 27 DLEs within the first four cycles including grade 4 thrombocytopenia (n = 5), prolonged grade 4 neutropenia (n = 2), febrile neutropenia (n = 2), and omission of day 8 gemcitabine (n = 18). There was one patient death secondary to a wound abscess and febrile neutropenia. Myelosuppression as expected was the dose-limiting toxicity. CONCLUSION: The schedule of paclitaxel 135 mg/m(2) (day 1, 3 h), carboplatin AUC 5 (day 1), and gemcitabine 800 mg/m(2) (days 1 and 8) is feasible, with an acceptable toxicity profile.     

A phase I trial of prolonged oral etoposide and liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a gynecologic oncology group study

OBJECTIVES: In an effort to explore second-line therapy in ovarian, peritoneal, and tubal carcinoma, a phase I trial combining prolonged oral etoposide and liposomal doxorubicin was conducted by the Gynecologic Oncology Group. METHODS: Liposomal doxorubicin (20 mg/m(2)) was administered intravenously over 1 h followed by oral etoposide at 50 mg/m(2)/day beginning on day 2. In the first phase of accrual, the number of days of oral etoposide was increased until its maximum tolerated dose (MTD) was determined based on hematologic toxicity. In the second phase, etoposide was given at the MTD while the dose of liposomal doxorubicin was escalated until its maximum tolerated dose was reached based on hematologic or nonhematologic toxicity. Cycles were repeated every 28 days for a maximum of 12 courses. Dose-limiting toxicity was defined as neutropenic sepsis, grade 4 thrombocytopenia, absolute neutrophil count <1000/microl or platelets <50,000 during treatment with etoposide, or > or =grade 3 mucositis/stomatitis, palmar-plantar erythrodyesthesia, or rash. RESULTS: Fifteen patients were accrued to the study's first phase, and 3 were accrued to the second phase. Dose-limiting hematologic toxicity occurred with 14 days of oral etoposide in combination with liposomal doxorubicin at 20 mg/m(2). Efforts to escalate the dose of liposomal doxorubicin to 30 mg/m(2) in combination with 12 days of oral etoposide at 50 mg/m(2) resulted in dose-limiting hematologic toxicity. Five of 17 (29%; 95% CI: 13-53%) evaluable patients experienced a response. CONCLUSION: The regimen of oral etoposide at 50 mg/m(2)/day for 12 days in combination with liposomal doxorubicin at a dose of 20 mg/m(2) is tolerable without supportive therapy. While this dose of oral etoposide has demonstrated activity as a single agent in ovarian cancer, liposomal doxorubicin has only been effective in ovarian cancer at higher doses. There are no immediate plans to study this combination further.     

Cisplatin plus gemcitabine in platinum-refractory ovarian or primary peritoneal cancer: a phase II study of the Gynecologic Oncology Group

OBJECTIVES: To evaluate the safety and efficacy of cisplatin plus gemcitabine in persistent or recurrent platinum-resistant ovarian and primary peritoneal cancer. STUDY DESIGN: Eligible, consenting subjects with measurable disease and one prior platinum-based regimen, but no prior gemcitabine, were to receive intravenous cisplatin followed by gemcitabine on days 1 and 8 every 28 days. RESULTS: Between December 2000 and March 2003, 59 patients were enrolled from 24 institutions; two were ineligible. During the first stage of accrual, 27 subjects received cisplatin 30 mg/m2 and gemcitabine 750 mg/m2. In the second stage, gemcitabine was reduced to 600 mg/m2 because of hematologic toxicity at the higher dose. There were 4 complete and 5 partial responses for an overall response rate of 16% (9/57). Thirty-one women (54%) had stable disease. Median time to progression was 5.4 months. Overall survival was 14.9+ months. Grade 4 toxicities were hematologic, except one cutaneous reaction. CONCLUSIONS: Cisplatin plus gemcitabine, in the doses and schedule employed, has modest activity in this patient population.     

A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma

Abstract.   Valerio MR, Tagliaferri P, Raspagliesi F, Fulfaro F, Badalamenti G, Arcara C, Cicero G, Russo A, Venuta S, Guarneri G, Gebbia N. A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 79–85
We carried out a phase II nonrandomized study to examine the level of activity of oxaliplatin, pegylated liposomal doxorubicin, and cyclophosphamide in a patient population with relapsed ovarian cancer pretreated with platinum derivatives and paclitaxel. Patients received oxaliplatin (85 mg/m²), pegylated liposomal doxorubicin (30 mg/m²), and cyclophosphamide (750 mg/m²). A total of 49 patients (39 assessable for toxicity and response) were enrolled in this trial. Neutropenia grade 3 was observed in six patients (15%) and anemia grade 3 in one patient (0.2%). Fatigue grade 1–2 occurred in 26 patients (66%), nausea/vomiting grade 1 in 23 patients (58%), and alopecia grade 1–2 in 19 patients (48%). Twenty-one (53%) patients experienced grade 1–2 peripheral neuropathy. The overall response rate was 46% (95% CI 23.6–68.7). Median progression-free survival was 28 weeks (range 12–52 weeks) and median survival was 45 weeks (range 26–136+ weeks). The mean duration of response was 34 weeks (range 16–52 weeks). In platinum-resistant and -refractory ovarian cancer patients, the overall response rate was 37% (CI 95% 14.4–60.8) with a progression-free survival of 28 weeks (range 12–52 weeks) and a median survival of 42 weeks (range 28–84 weeks). This combination chemotherapy is generally well tolerated and is an active second-line regimen against ovarian cancer.     

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Objective

To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods

Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m² on day 8. A standard 3 + 3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results

Patients were treated with paclitaxel 175 mg/m² IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m² IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), > 2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m² IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).

Conclusions

Paclitaxel at 175 mg/m² IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m² IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.     

Retrospective comparative study of irinotecan and pegylated liposomal doxorubicin for platinum-resistant or -refractory epithelial ovarian and primary peritoneal carcinoma

Purpose

This study was conducted to retrospectively compare the efficacy and safety of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant or -refractory recurrent epithelial ovarian and primary peritoneal carcinoma.

Methods

Nineteen patients who received CPT-11 and eleven patients who received PLD were enrolled. CPT-11 was intravenously administered at a starting dose of 60–100 mg/m² on day 1, 8, and 15 every 28 days, and PLD was administered at a starting dose of 40–50 mg/m² on day 1 every 28 days. Primary outcomes were overall response rate (complete response [CR] + partial response [PR]), disease control rate (CR + PR + stable disease), and progression-free survival (PFS) in each group. Clinical response was evaluated every two or three cycles using the Response Evaluation Criteria in Solid Tumors criteria; CA125 analysis was not performed.

Results

The overall response rate was 21.1 % (PR, four cases) and 0 % (p = 0.10) in the CPT-11 and PLD groups, respectively, and the disease control rate was 73.7 and 45.5 % (p = 0.12), respectively. Median PFS was 25.3 (range 5.4–69.9) weeks and 12.7 (range 4.0–43.1) weeks in the CPT-11 and PLD groups, respectively; however, this difference was not statistically significant (p = 0.064). Major adverse events in the CPT-11 group were neutropenia, nausea, and diarrhea, whereas those in the PLD group included thrombocytopenia, anemia, stomatitis, and hand-foot syndrome.

Conclusions

This retrospective study demonstrated comparable efficacy outcomes for CPT-11 and PLD. The overall response rate, disease control rate, and median PFS were more favorable in the CPT-11 group compared to the PLD group, although the difference was not significant. The adverse event profiles were different between groups. These results suggest that CPT-11 might be a feasible choice as single-agent salvage chemotherapy for platinum-resistant or -refractory recurrent epithelial ovarian and primary peritoneal carcinoma beside established regimen like PLD.     

A phase II trial of CI-958 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study

OBJECTIVES: To estimate the antitumor efficacy of CI-958 in patients with measurable recurrences of platinum-sensitive ovarian carcinoma and to determine the nature and degree of toxicity of CI-958 in these patients. METHODS: Patients received CI-958 560 mg/m2 intravenously every 3 weeks and tumor measurements were performed every one to two cycles. RESULTS: Of 23 patients entered in the study, there was one complete response and 10 patients had stable disease with short response durations. CONCLUSIONS: CI-958 has minimal activity in recurrent platinum-sensitive ovarian carcinoma at the dose and schedule tested.     

A phase II trial of dolastatin-10 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study

OBJECTIVE: To estimate the antitumor efficacy of dolastatin-10 in patients with measurable recurrences of platinum-sensitive ovarian carcinoma and to determine the nature and degree of toxicity of dolastatin-10 in these patients. METHODS: Patients received dolastatin-10 400 microg/m(2) intravenously every 3 weeks and tumor measurements were performed every one to two cycles. RESULTS: Of 28 patients evaluable for response, there were no complete or partial responses. Seven patients had stable disease and 21 patients had increasing disease. CONCLUSION: Dolastatin-10 has minimal activity in recurrent platinum-sensitive ovarian carcinoma at the dose and schedule tested.     

A multicenter phase II study of pegylated liposomal doxorubicin and oxaliplatin in recurrent ovarian cancer

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) and oxaliplatin (LOHP) are active as single agents in the treatment of recurrent ovarian cancer (ROC). This phase II study investigated the safety and activity of PLD and LOHP used in combination to treat ROC. METHODS: Eligibility criteria included disease recurrence after one (45%) or more lines (55%) of chemotherapy, performance status 3 months. Treatment was 40 mg/m(2) PLD and 120 mg/m(2) LOHP, administered over 2 days, every 3 weeks. Response to therapy was assessed using the RECIST criteria. RESULTS: Forty patients with ROC enrolled in the study from 10/2001 to 10/2005; 27 patients were platinum-sensitive and 13 were platinum-resistant. Major toxicities included grade 3-4 neutropenia (37%) and grade 2 palmar-plantar erythrodysesthesia (10%). The overall response rate was 67.5%, with 30% stable disease rate and 2.5% progressive disease rate. The median progression-free survival (PFS) was 9.6 months, while median overall survival was 18.3 months, with no statistically significant difference in PFS between platinum-resistant and platinum-sensitive patients. CONCLUSION: We conclude that the combination of PLD and LOHP shows activity in ROC with a manageable toxicity profile and can be safely administered in heavily pre-treated patients.     

A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer

Objective

To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer.

Methods

Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m² and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10 mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete + partial response]; additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP).

Results

Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4, 83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable) and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6 %) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had ≥ 1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed.

Conclusion

Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer.