Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer

Figures & data

Table 1. HIPEC in ovarian cancer studies as first line treatment during primary cytoreductive surgery presented in more relevant publications.

Study	No. of Patients	Drug	Morbidity (%)	Mortality (%)	Median PFS months	Median OS months	5-year OS (%)	Median FU
Ansaloni et al. (2012) [56]	39	Cisplatin + paclitaxel (11) Cisplatin + doxorubicin (26) Paclitaxel + doxorubicin (1) Doxorubicin (1)	18	2.6	14	NR	NR	NR
Bakrin et al. (2013) [57]	92	Cisplatin; Doxorubicin; Oxaliplatin; Mitomycin Cisplatin + mitomycin Cisplatin + doxorubicin	31 ≥grade III	1	12	35	17	40
Carrabin et al. (2010) [58]	12 (8)	Oxaliplatin	56 grade III	0	17	NR	NR	38
Cascales Campos et al. (2011) [59]	35	Paclitaxel (32) Cisplatin (3)	13 grade III, 2 grade IV	0	NR	NR	NR	NR
Cascales Campos et al. (2014) [60]	52	Paclitaxel	NR	NR	63% at 3 years	NR	NR	NR
Coccoloni et al. (2015) [61]	54	Cisplatin; Paclitaxel	35 grade III/IV	6	12	33	NR	20
Deraco et al. (2011) [62]	26	Cisplatin + doxorubicin	15	4	30	NR	61	25
Di Giorgio et al. (2008) [63]	22	Cisplatin	21	4	20	24	17	NR
Frenel et al. (2011) [64]	19	Oxaliplatin	29 grade III; 3 grade IV	NR	13	NR	NR	14
Helm et al. (2010) [65] (HYPER-O)	26	Cisplatin + carboplatin + mitomycin combination	NR	0.5	25	42	33	18
Helm et al. (2010) [65] (HYPER-O)	19	Cisplatin + carboplatin + mitomycin combination	NR	0.5	17	69	50	18
Kim et al. (2010) [66]	19	Paclitaxel	16 grade III	0	NR	NR	84	80
Lim et al. (2009) [67]	30	Cisplatin	40 grade III	0	NR	NR	NR	NR
Pavlov et al. (2009) [68]	31	Doxorubicin + cisplatin	18	2	NR	34	55	60
Pomel et al. (2010) [69]	31	Oxaliplatin	3	0	NR	NR	67 (2 years)	NR
Rettenmaier et al. (2015) [70]	37	Carboplatin	16 grade III/IV	0	13	14	NR	NR
Roviello et al. (2010) [71]	14	Cisplatin + mitomycin	23 grade III, 4 grade IV	0	NR	NR	55	27
Roviello et al. (2010) [71]	31	Cisplatin + mitomycin	23 grade III; 4 grade IV	0	NR	NR	58	27
Rufian et al. (2006) [72]	19	Paclitaxel	36	0	25	38	37	NR

FU, follow-up; NR, not reported, OS, overall survival.

Studies by Ansaloni et al. [73], and Coccoloni et al. [74] also separately present groups of patients with recurrence ovarian cancer. Studies by Frenel et al. [75], Kim et al. [76], Pommel et al. [77], and trials by Ansaloni et al. [78] present HIPEC in ovarian cancer as a variant with consolidation treatment. Studies by Carrabin et al. [79], Helm et al. [80], and Roviello et al. [81] present patients with HIPEC during interval cytoreductive surgery.

Table 2. HIPEC as a treatment in recurrence OC presented in more relevant publications and ongoing trials.

Study	No. of patients	Type of recurrence	Morbidity (%)	Mortality (%)	Median PFS	Median OS	5-year OS (%)	Median FU
Argenta et al. (2013) [82]	10	Previous optimal tumour cytoreduction (< 1 cm) followed by platinum and taxane-based adjuvant chemotherapy; platinum sensitive disease, defined as > 6 months since their last chemotherapy administration	2 grade IV	0	NR	NR	NR	16
Bae et al. (2007) [83]	44	HIPEC during ‘secondary surgery’	NR	NR	56	NR	66	NR
Bakrin et al. (2013) [57]	474	Chemoresistant 247 Chemosensitive EOC : recurrence in 223; 4 undetermined	31 ≥grade III	1	NR	46	37	40
Carrabin et al. (2010) [58]	10	1 platin resistant; All had 1–3 lines of previous chemotherapy	56 grade III/IV	0	10	NR	NR	38
Cascales Campos et al. (2014) [60]	32	No information	21 grade III/IV	NR	45% at 3 years	NR	NR	18
Ceelen et al. (2012) [84]	42	17 patients (41%) were platin resistant	21	0	13	37	42	21
Cotte et al. (2007) [85]	81	16 chemoresistant, 4 with large-volume residual tumours following 1st-line chemo, 12 with recurrence after PFI < 6 months); 65 had recurrent lesions, 8 with 1st recurrence after PFI 6–18 months; 57 after 2nd or 3rd recurrence. 29/57 had 2nd recurrence, 20 had 3rd or 4th recurrence, 8 had ≥5 recurrences >4 years after initial treatment	14	2	19	28	NR	47
de Bree et al. (2003) [84]	19	Patients with early recurrence (<6 months after chemotherapy), or persistent carcinomatosis after primary systemic chemotherapy	58	11	26	54	42	21
Deraco et al. (2012) [85]	56	23% of patients (13) were platinum resistant	26 major complications	5	19	28	NR	47
Di Giorgio et al. (2008) [86]	25	All 1 or more operations for OC (range 1–4 laparotomies)+chemo (range 1–3 lines). 18 recurrent disease, 4 interval debulking, 3 2nd-look surgery	21	4	26	54	42	30
Fagotti et al.(2011) [63]	41	All patients were platinum sensitive	35	0	11	26	23	23
Frenel et al.(2011) [87]	12	75% 1st relapse, 17% 2nd, 8% 3rd relapse	29 grade III 3 grade IV	0	20	24	17	NR
Gori et al. (2005) [51]	29	HIPEC during ‘secondary surgery’	NR	0	24	38	NR	38
Helm et al. (2010) [64] (HYPER-O)	83	78/83 patients received before platinum chemo, 76 platinum sensitive	NR	0,5	14	24	18	23
Helm et al. (2007) [88]	18	Mean prior laparotomies 1.4 (0–3), mean chemotherapy agents 3.2 (0–7) 2 had previous pelvic radiotherapy. 8 platinum resistant (44%)	28 ≥grade III haematological 72 ≥grade III metabolic/other	6	57	64	NR	64
Le Brun et al. (2014) [65]	23	Only 1st relapse patients, >6 months after the end of the initial treatment 1st and 2nd line chemo always given	NR	0	14	24	18	18
Koningsrainer et al. (2014) [89]	90	47% preoperative chemo, 13% platin resistant	42	0	10	31	NR	20
Muñoz-Casares et al (2009) [90]	14	No detailed information	20	0	24	NR	76 (4 years)	24
Massari et al. (2014) [52]	11	All patients previously had surgery and chemo	16	8	NR	35 vs 14 (CC0/1 vs 2/3)	NR	19
Pavlov et al. (2009) [91]	25	No detailed information	18	2	48	NR	58	NR
Piso et al. (2004) [92]	11	10 platin-based chemo, (3 with taxanes), and 1 with only taxanes	36	5	12	27	NR	NR
Raspagliesi et al. (2006) [68]	40	13 presented partial response to 1st-line chemo and treated in a 2nd-look setting. 27 had advanced relapsing disease and had received a median 2 lines (range 1–5) of systemic chemo, of cisplatin, taxol or taxol/platinum	20	0	NR	40	72	60
Robella et al (2014) [93]	25	No detailed information	36	7	NR	47	27	20
Rufian et al. (2006) [42]	14	Patients were previously treated by surgery with/without chemo	36	0	24	41	15	26
Ryu et al. (2004) [41]	35	Positive partial response after platin-based chemo after previous operation	36	0	49	72	63	NR
Ryu et al. (2004) [41]	26	HIPEC during ‘secondary surgery’	NR	NR	41	NR	55	NR
Safra et al. (2014) [45]	27	All patients were platin sensitive	NR	NR	15	NR	79	NR
Zanon et al. (2004) [95]	30	8 previously treated with systemic chemo alone had hysterectomy, ovariectomy, and omentectomy during cytoreductive surgery. 13/22 who had had primary surgery had had 1 line previous systemic chemo and 9 had had 2 or more	17	3	17	28	NR	19

FU, follow-up; chemo, chemotherapy; PFI, progression-free interval; NR, not reported; PFS, progression-free survival; OS, overall survival.

Table 3. Selected ongoing trials for HIPEC in ovarian cancer.

Clinical trial identifier	Patient no.	Disease status	Primary end point	Drug	Status
NCT02124421	48	Primary CRS	Assess the feasibility of recruitment compare complication rates	Carboplatin, paclitaxel, cisplatin	Recruiting
NCT01091636	170	Primary CRS	Progression-free survival; assess progression-free survival rate for 2 years after HIPEC with adjuvant treatment	Cisplatin	Recruiting
NCT01628380	94	HIPEC consolidation treatment	Disease free survival	Cisplatin + paclitaxel	Recruiting
NCT02328716	32	Primary CRS	Disease-free survival	Cisplatin	Ongoing not recruiting
NCT01709487	24	Primary CRS	Mortality rate	Cisplatin	Recruiting
NCT02249013	20	Primary CRS	Progression-free survival	Cisplatin	Recruiting
NCT02199171	30	Primary CRS	Maximum tolerated dose, adverse events	Carboplatin	Recruiting
NCT02217956	30	HIPEC consolidation treatment	Toxicity	Cisplatin, bevacizumab	Recruiting
NCT02567253	48	Primary and recurrent OC	Tissue penetration distance of cisplatin in peritoneal tumour tissue nodules using laser-ablation inductively coupled plasma mass spectrometry	Cisplatin	Not open
NCT00426257	280	HIPEC during secondary surgery	Duration of recurrence free survival	Cisplatin	Recruiting
NCT01539785	158	HIPEC in recurrent OC	Estimate of progression free interval	Cisplatin	Recruiting
NCT01767675	98	HIPEC in recurrent OC	Estimate of progression free interval	Carboplatin	Recruiting
NCT01376752	444	HIPEC in recurrent OC	Overall survival	Cisplatin	Recruiting
NCT01970722	50	HIPEC in primary or recurrent OC with/without normothermic post-operative intraperitoneal chemo	Treatment-related toxicities	Different for specific cancer	Recruiting
NCT01588964	30	HIPEC in recurrent OC	Progression free survival, overall survival, post-operative complications, efficacy and tolerability of the treatment	Oxaliplatin	Study completed
NCT02217956	30	HIPEC consolidation treatment	Toxicity	Cisplatin	Recruiting

OC, ovarian cancer; CRS, cytoreductive surgery.

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