Table 2.
Review of intraperitoneal chemotherapy trials in recurrent ovarian cancer.
| Study (Level of Evidence) | Cohorts | Drugs | Results |
|---|---|---|---|
| Cascales Campos, 2011, Level III [39] | Descriptive study of outcomes in both primary and recurrent epithelial ovarian cancer who had been treated with optimal CRS (CC-0 or CC-1) + HIPEC | ● Cytostatic paclitaxel: 60 mg/m2 ● In taxol allergic patients: 75 mg/m2 cisplatin ● 60 min at 42–43 °C |
● Median operative time 380 mins ● CC-0 achieved in 38/46 patients ● Major morbidity 15.3% with ileus being most common ● Mean operative stay 6.9 days ● No mortality |
| Fagotti, 2012, Level III [40] | Case-control ● CRS + HIPEC (n = 30) ● CRS without HIPEC (n = 37) Platinum-sensitive recurrent epithelial ovarian cancer patients |
● Oxaliplatin: 460 mg/m2
● 30 min at 41.5 °C ● Systemic platinum-based chemo afterwards |
Primary outcome: progression-free survival ● HIPEC: 26 months ● Non-HIPEC: 15 mos 5 year overall survival: ● HIPEC: 68.4% ● Non-HIPEC: 42.7% CC-0 reached in 96.7% Median time to systemic CT = 40 days (no diff) HIPEC toxicity in 35%, 0% 30 day mortality |
| Bakrin, 2012, Level III [41] | ● Platinum sensitive (n = 184) ● Platinum resistant (n = 62) Multicenter prospective study of outcomes in recurrent epithelial ovarian cancer who had been treated with optimal CRS + HIPEC |
● 95.5% used cisplatin alone or in combination with doxorubicin or mitomycin C ● 90 min from 44–46 °C inflow temperature |
Primary outcome: grade III-IV complications ● 11.6% complications Overall median survival: 48 months in platinum-resistant and 52 months in platinum-sensitive (p = 0.568) |
| Safra, 2014, Level III [42] | Retrospective case control ● CRS + HIPEC + Systemic CT (n = 27) ● CRS + systemic CT only (n = 84) Recurrent ovarian cancer patients, stratified by BRCA gene mutation status |
● Cisplatin 50 mg/m2 + doxorubicin 15 mg/m2 ● Paclitaxel 60 mg/m2 + carboplatin AUC 4 ● Cisplatin 25 mg/l/m2 + mitomycin-C 3.3 mg/l/m2 ● 120 min at 42.5 °C |
Primary outcome: median progression free survival ● HIPEC: 15 months ● Non-HIPEC: 6 months Secondary outcome: BRCA status progression free survival ● BRCA HIPEC: 20.9 months ● BRCA non-HIPEC: 12.6 months 5 year survival: ● HIPEC: 79% ● Systemic CT: 45% |
| Cascales Campos, 2014, Level III [32] | Retrospective case control study before and after introducing HIPEC in 2008 ● Before (n =22) ● After (n = 32) |
● Cytostatic paclitaxel: 60 mg/m2
● In taxol allergic patients: 75 mg/m2 cisplatin ● 60 min at 42–43 °C |
Primary outcome: Progression-free survival ● Before- 77% at 1 yr, 23% at 3 yr ● After- 77% at 1 yr, 45% at 3 yr Non-significant differences in PFS No significant differences in morbidity (23% before, 28% after) |
| Le Brun, 2014, Level III [43] | Retrospective multicenter case-control study Recurrent ovarian cancer patients ● CRS + HIPEC (n = 23) ● CRS + Control (n = 19) |
● Cisplatin: 16 mg/m2 ● Eloxatin 6 mg/m2 ● Mitomycin 1 mg/m2 ● 42 °C ● Cisplatin 60 min, other two 30 min |
Overall survival at 4 years ● HIPEC: 75.6% ● Control: 19.4% CC-0 rate 100% No mortality Mean length of stay ● HIPEC: 17 days ● Control: 11 days |
| Delott, 2015, Level III [44] | Retrospective single-center review looking at morbidity and survival in elderly patients (n = 15) Age >70 years (median age 72) Relapsed ovarian cancer with peritoneal carcinomatosis |
● Cisplatin 50 mg/m2 + doxorubicin 15 mg/m2 ● 60 min at 43 °C |
● Progression-free survival: 15.6 months ● Medial overall survival: 35 months ● CC-0 in 9/15 cases, CC-1 in 6/15 ● Grade 3–4 in 20% of patients ● Median length of stay: 13 days (average 20) |
| Spiliotis, 2015, Level I [45] | Prospective randomized controlled trial ● CRS + HIPEC + Systemic CT (n = 60) ● CRS + Systemic CT (n = 60) Recurrent stages IIIC-IV epithelial ovarian cancer |
● Platinum-sensitive: cisplatin 100 mg/m2 + paclitaxel 175 mg/m2
● Platinum-resistant: doxorubicin 35 mg/m2 + paclitaxel 175 mg/m2 or mitomycin 15 mg/m2 ● 60 min at 42.5 °C |
Primary outcome: mean overall survival ● HIPEC: 26.7 mos ● Non-HIPEC: 13.4 mos No statistical difference between platinum-resistant and -sensitive in HIPEC group CC-0 in 65% HIPEC, 55% control CC-1 in 20% HIPEC, 33.3% control |
| Petrillo, 2016, Level III [46] | Retrospective review of 5 and 7 year survival outcomes with median follow up of 73 months in 70 patients Recurrent platinum-sensitive disease who had undergone CRS + HIPEC |
● Oxaliplatin 460 mg/m2 in 43 cases for 30 min ● Cisplatin 75 mg/m2 in 17 cases for 60 min ● 41.5 °C ● Systemic platinum + taxane postoperatively |
● CC-0 in 88.6%, CC-1 in 11.4% ● Median progression-free survival 27 months ● 5 year survival: 52.8% ● 7 year survival: 44.7% ● 30 day complication rate: 35.7% with two grade 3, and four grade 4 |