Table 1.
Anti-VEGF angiogenic inhibitors in ovarian cancer.
| Targeted agent | Chemotherapeutic agent | Dosing schedule | Phase | Participants (n) | Results | Adverse effects | Ref. |
|---|---|---|---|---|---|---|---|
| Bevacizumab | − | Bevacizumab 15 mg/kg iv. every 21 days until disease progression | II | 62 | Median PFS and OS were 4.7 and 17 months, respectively | Hypertension, vomiting, thromboembolism, dyspnea | [17] |
| Bevacizumab | − | Bevacizumab 15 mg/kg iv. every 21 days | II | 44 | Median PFS and OS was 4.4 and 10.7 months, respectively | Hypertension, proteinuria, bleeding | [18] |
| Bevacizumab | Cyclophosphamide | Bevacizumab 10 mg/kg iv. every 2 weeks and oral cyclophosphamide 50 mg/day | II | 70 | Median time to PFS and OS were 7.2 and 16.9 months, respectively | Hypertension, fatigue, pain, GIT bleeding | [19] |
| Bevacizumab | Irinotecan | Bevacizumab 5 mg/kg iv. every 2 weeks + irinotecan 60 mg/m2 weekly, repeated every 28 days, up to six cycles | II | 52 | Stable disease 42.3%, median PFS and OS were 8.0 and 13.8 months, respectively | Diarrhea, neutropenia, thrombocytopenia | [20] |
| Bevacizumab | Paclitaxel + carboplatin | Bevacizumab 7.5 mg/kg + paclitaxel 80 mg/m2 weekly + carboplatin AUC 6 iv. every 28 days for 6–8 cycles → bevacizumab for 1 year | II | 189 | Median PFS of 23.7 months, 1-year PFS of 85.6%, RR of 84.6% | Febrile neutropenia, thrombocytopenia, neuropathy | [21] |
| Bevacizumab | Oxaliplatin + docetaxel | Six cycles of oxaliplatin 85 mg/m2 + docetaxel 75 mg/m2 + bevacizumab 15 mg/kg every 3 weeks → bevacizumab 15 mg/kg every 3 weeks for 1 year | II | 132 | RR of 58.6%, median PFS and OS were 16.3 and 47.3 months, respectively | Neutropenia, leukopenia, hypertension, fatigue | [22] |
| Bevacizumab | Gemcitabine + carboplatin | Gemcitabine 1000 mg/m2 + carboplatin AUC 3 + bevacizumab 10 mg/kg iv. every 2 weeks for 6 cycles or up to 24 cycles if clinical benefit occurred | II | 45 | RR of 69%, median PFS of 13.3 months | Hypertension, fatigue | [23] |
| Sunitinib | − | Sunitinib 50 mg/day for 28 days followed by 14 days off drug | II | 73 | Median PFS and OS were 4.8 and 13.6 months, respectively | GIT bleeding, fatigue, nausea | [24] |
| Sunitinib | − | Sunitinib 50 mg/day, 4 of 6 weeks | 30 | Stable disease in 53%, five had >30% decrease in measurable disease, median PFS of 4.1 months | Fatigue, gastrointestinal symptoms, hand–foot syndrome, hypertension | [25] | |
| Sorafenib | − | Sorafenib 400 mg b.i.d | II | 71 | Two patients had partial response, 20 had stable disease, median PFS of 6 months | Rash, hand-foot syndrome, metabolic and GIT abnormalities | [26] |
| Sorafenib | − | Sorafenib 400 mg b.i.d | II | 246 | Median PFS of 12.7 months | Rash, hand–foot syndrome | [27] |
| Cediranib | Paclitaxel + carboplatin | Carboplatin AUC 5/6 + paclitaxel 175 mg/m2 + cediranib 20 mg/day followed by placebo (concurrent) or cediranib 20 mg/ day | 60 | 49 patients completed 6 cycles of chemotherapy | Diarrhea, hypertension, fatigue, rash | [28] | |
| BOOST (NCT01462890) | Paclitaxel + carboplatin | Bevacizumab 15 mg/kg, iv. and paclitaxel + carboplatin 175 mg/m2 iv. every 3 weeks | III | − | Ongoing | − | |
| MITO-16/ MANGO-2b (NCT01802749) | Paclitaxel, carboplatin | Bevacizumab 15 mg/kg, iv. and paclitaxel + carboplatin 175 mg/m2 iv. every 3 weeks | III | − | Ongoing | − | |
| GOG-0213 (NCT00565851) | Paclitaxel, carboplatin, gemcitabine hydrochloride | Paclitaxel + carboplatin/gemcitabine hydrochloride 175 mg/m2 iv. + bevacizumab 15 mg/kg iv. every 3 weeks | III | − | Ongoing | − | |
| PAZPET-1 (NCT01608009) | Paclitaxel | Pazopanib 800 mg q.d for 7 days → paclitaxel 80 mg/m2 weekly + pazopanib 800 mg q.d for 18 weeks → maintenance pazopanib 800 mg q.d until disease progression | III | − | Ongoing | − | |
| Carbo-Cox-2 (NCT01124435) | Carboplatin | Celecoxib 200 mg b.i.d for 28 days + carboplatin AUC 5 every 28 days | II | − | Ongoing | − | |
| Pazopanib (NCT00866697) | − | Pazopanib 800 mg daily for 24 months | III | − | Ongoing | − | |
| Sunitinib (NCT00768144) | − | Sunitinib 37.5 mg/day for 28 days | II | − | Ongoing | − | |
AUC: Area under curve; b.i.d: Two-times a day; GIT: Gastrointestinal; iv.: Intravenous; PFS: Progression-free survival; q.d: Once a day; OS: Overall survival; RR: Response rate.