Chemotherapy

Paclitaxel. Treatment with paclitaxel historically provided the first agent with consistent activity in patients with platinum-refractory or platinum-resistant recurrences.[47-51] Patients generally received paclitaxel in front-line induction regimens. Re-treatment with paclitaxel, particularly in weekly schedules, had activity comparable with that of other drugs. Residual neuropathy upon recurrence may shift the choice of treatment towards other agents.

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan):

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan):

Topotecan was compared with pegylated liposomal doxorubicin in a randomized trial of 474 patients and demonstrated similar response rates, PFS, and OS at the time of the initial report. Responses occurred primarily in the platinum-resistant subsets.[53]

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan):

In phase II studies, topotecan administered intravenously (IV) on days 1 to 5 of a 21-day cycle yielded objective response rates ranging from 13% to 16.3% and other outcomes that were equivalent or superior to paclitaxel.[54-56]

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan): › In phase II studies, topotecan administered intravenously (IV) on days 1 to 5 of a 21-day cycle yielded objective response rates ranging from 13% to 16.3% and other outcomes that were equivalent or superior to paclitaxel.[54-56]

Objective responses were reported in patients with platinum-refractory disease.

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan): › In phase II studies, topotecan administered intravenously (IV) on days 1 to 5 of a 21-day cycle yielded objective response rates ranging from 13% to 16.3% and other outcomes that were equivalent or superior to paclitaxel.[54-56]

Substantial myelosuppression followed administration. Other toxic effects included nausea, vomiting, alopecia, and asthenia. Some schedules and oral formulations to reduce toxicity are under evaluation.

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan):

In a phase III study, 235 patients who did not respond to initial treatment with a platinum-based regimen, but who had not previously received paclitaxel or topotecan, were randomly assigned to receive either topotecan as a 30-minute infusion daily for 5 days every 21 days or paclitaxel as a 3-hour infusion every 21 days.[52][Level of evidence B1]

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan): › In a phase III study, 235 patients who did not respond to initial treatment with a platinum-based regimen, but who had not previously received paclitaxel or topotecan, were randomly assigned to receive either topotecan as a 30-minute infusion daily for 5 days every 21 days or paclitaxel as a 3-hour infusion every 21 days.[52][Level of evidence B1]

The overall objective response rate was 20.5% for patients who were randomly assigned to treatment with topotecan and 13.2% for patients who were randomly assigned to treatment with paclitaxel (P = .138).

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan): › In a phase III study, 235 patients who did not respond to initial treatment with a platinum-based regimen, but who had not previously received paclitaxel or topotecan, were randomly assigned to receive either topotecan as a 30-minute infusion daily for 5 days every 21 days or paclitaxel as a 3-hour infusion every 21 days.[52][Level of evidence B1]

Both groups experienced myelosuppression and gastrointestinal (GI) toxic effects. Nausea and vomiting, fatigue, and infection were observed more commonly after treatment with topotecan, whereas alopecia, arthralgia, myalgia, and neuropathy were observed more commonly after treatment with paclitaxel.[52]

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan):

The combination of weekly topotecan and biweekly bevacizumab was evaluated in a phase II study.

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan): › The combination of weekly topotecan and biweekly bevacizumab was evaluated in a phase II study.

Results showed an objective response rate of 25% (all partial responses) in a platinum-resistant patient population.[57]

Topotecan. Randomized studies have indicated that the use of topotecan achieved results that were comparable with those achieved with paclitaxel.[52] Evidence (topotecan): › The combination of weekly topotecan and biweekly bevacizumab was evaluated in a phase II study.

The most common grade 3 and grade 4 toxicities were hypertension, neutropenia, and GI toxicity, although no bowel perforations occurred.

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin):

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin):

In a phase II study encapsulated doxorubicin was given IV once every 21 to 28 days.[58]

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin): › In a phase II study encapsulated doxorubicin was given IV once every 21 to 28 days.[58]

Results demonstrated one complete response and eight partial responses in 35 patients with platinum-refractory or paclitaxel-refractory disease (response rate, 25.7%).

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin): › In a phase II study encapsulated doxorubicin was given IV once every 21 to 28 days.[58]

In general, liposomal doxorubicin has few acute side effects other than hypersensitivity. The most frequent toxic effects (stomatitis and hand-foot syndrome) were usually observed after the first cycle and were more pronounced after dose rates exceeded 10 mg/m2 per week. Neutropenia and nausea were minimal, and alopecia rarely occurred.

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin):

Pegylated liposomal doxorubicin and topotecan have been compared in a randomized trial of 474 patients with recurrent ovarian cancer.[53][Level of evidence A1]

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin): › Pegylated liposomal doxorubicin and topotecan have been compared in a randomized trial of 474 patients with recurrent ovarian cancer.[53][Level of evidence A1]

Response rates (19.7% vs. 17.0%; P = .390), PFS (16.1 weeks vs. 17.0 weeks; P = .095), and OS (60 weeks vs. 56.7 weeks; P = .341) did not differ significantly between the pegylated liposomal doxorubicin and topotecan arms.[53][Level of evidence A1]

Pegylated liposomal doxorubicin. Evidence (pegylated liposomal doxorubicin): › Pegylated liposomal doxorubicin and topotecan have been compared in a randomized trial of 474 patients with recurrent ovarian cancer.[53][Level of evidence A1]

Survival was longer for the patients with platinum-sensitive disease who received pegylated liposomal doxorubicin.[21]

Docetaxel. This drug has shown activity in paclitaxel-pretreated patients and is a reasonable alternative to weekly paclitaxel in the recurrent setting.[59]

Gemcitabine. Gemcitabine is an antimetabolite that was developed and approved in combination with platinum-based chemotherapy drugs and has shown activity as a single agent. Gemcitabine combined with cell cycle−targeted drugs and other drug combinations used in indications such as pancreatic and lung cancers are being explored.[60-63] Evidence (gemcitabine):

Gemcitabine. Gemcitabine is an antimetabolite that was developed and approved in combination with platinum-based chemotherapy drugs and has shown activity as a single agent. Gemcitabine combined with cell cycle−targeted drugs and other drug combinations used in indications such as pancreatic and lung cancers are being explored.[60-63] Evidence (gemcitabine):

Several phase II trials of gemcitabine as a single-agent–administered IV on days 1, 8, and 15 of a 28-day cycle have been reported.[60-62]

Gemcitabine. Gemcitabine is an antimetabolite that was developed and approved in combination with platinum-based chemotherapy drugs and has shown activity as a single agent. Gemcitabine combined with cell cycle−targeted drugs and other drug combinations used in indications such as pancreatic and lung cancers are being explored.[60-63] Evidence (gemcitabine): › Several phase II trials of gemcitabine as a single-agent–administered IV on days 1, 8, and 15 of a 28-day cycle have been reported.[60-62]

The response rate ranged from 13% to 19% in evaluable patients.

Gemcitabine. Gemcitabine is an antimetabolite that was developed and approved in combination with platinum-based chemotherapy drugs and has shown activity as a single agent. Gemcitabine combined with cell cycle−targeted drugs and other drug combinations used in indications such as pancreatic and lung cancers are being explored.[60-63] Evidence (gemcitabine): › Several phase II trials of gemcitabine as a single-agent–administered IV on days 1, 8, and 15 of a 28-day cycle have been reported.[60-62]

Responses have been observed in patients whose disease was platinum refractory and/or paclitaxel refractory as well as in patients with bulky disease.

Gemcitabine. Gemcitabine is an antimetabolite that was developed and approved in combination with platinum-based chemotherapy drugs and has shown activity as a single agent. Gemcitabine combined with cell cycle−targeted drugs and other drug combinations used in indications such as pancreatic and lung cancers are being explored.[60-63] Evidence (gemcitabine): › Several phase II trials of gemcitabine as a single-agent–administered IV on days 1, 8, and 15 of a 28-day cycle have been reported.[60-62]

Leukopenia, anemia, and thrombocytopenia were the most common toxic effects. Many patients reported transient flu-like symptoms and a rash after drug administration. Other toxic effects, including nausea, were usually mild.

Gemcitabine. Gemcitabine is an antimetabolite that was developed and approved in combination with platinum-based chemotherapy drugs and has shown activity as a single agent. Gemcitabine combined with cell cycle−targeted drugs and other drug combinations used in indications such as pancreatic and lung cancers are being explored.[60-63] Evidence (gemcitabine):

A randomized trial of gemcitabine versus pegylated liposomal doxorubicin showed noninferiority and no advantage in therapeutic index of one drug over the other.[63]

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed):

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed):

A randomized, double-blinded phase II European trial with 102 patients evaluated pemetrexed at two doses: standard-dose (500 mg/m2) versus high-dose (900 mg/m2) IV every 3 weeks.[66]

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed): › A randomized, double-blinded phase II European trial with 102 patients evaluated pemetrexed at two doses: standard-dose (500 mg/m2) versus high-dose (900 mg/m2) IV every 3 weeks.[66]

The response rate was 9.3% for the standard dose and 10.4% for the high dose.

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed): › A randomized, double-blinded phase II European trial with 102 patients evaluated pemetrexed at two doses: standard-dose (500 mg/m2) versus high-dose (900 mg/m2) IV every 3 weeks.[66]

The toxicity profile favored the standard dose, with fatigue, nausea, and vomiting as the most common severe toxicities.

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed):

A phase II study by the GOG utilized pemetrexed (900 mg/m2) IV every 3 weeks in 51 patients with platinum-resistant recurrent disease.[67]

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed): › A phase II study by the GOG utilized pemetrexed (900 mg/m2) IV every 3 weeks in 51 patients with platinum-resistant recurrent disease.[67]

The response rate was 21% in a heavily pretreated population in which 39% of the patients had received five or more regimens previously.

Pemetrexed. Pemetrexed combined with gemcitabine has had unconvincing results compared with either agent alone.[64,65] More studies are forthcoming that target cell cycle derangements common in certain genomic subtypes of ovarian cancer. Specifically, gemcitabine is presumed to be more active when there is loss of G1/S checkpoint from TP53 variants, CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation. Evidence (pemetrexed): › A phase II study by the GOG utilized pemetrexed (900 mg/m2) IV every 3 weeks in 51 patients with platinum-resistant recurrent disease.[67]

Myelosuppression and fatigue were the most common severe toxicities.