Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer

Table 1 Baseline characteristics of the study patients n (%)

Demographics	Total (n = 38)	Adjuvant group (Group 1, n = 25)	Neoadjuvant group (Group 2, n = 13)
Median age (yr)	55.5	54.3	50.1
Range	38.6-73.8	42.1-68.8	38.6-73.8
Age groups
30-50	16	10	6
51-60	10	8	2
61-75	12	7	5
Primary site
Ovarian	37 (97)	24 (96)	13 (100)
Fallopian tube	1 (3)	1 (4)	0 (0)
Tumor stage
IIB	1 (2.6)	0 (0)	1 (7.7)
IIC	2 (5.3)	2 (8)	0 (0)
IIIA	3 (7.9)	2 (8)	1 (7.7)
IIIB	5 (13.2)	4 (16)	1 (7.7)
IIIC	22 (57.9)	14 (56)	8 (61.5)
IV	2 (5.3)	0 (0)	2 (15.4)
Recurrent (n = 3)	3 (7.9)
IIB/C	2 (8)	2 (8)	0 (0)
IIIB	1 (2.6)	1 (2.6)	0 (0)
Histology
High grade serous	37 (97.3)	25 (100)	12 (93.3)
Poorly differentiated	1 (2.7)	0 (0)	1 (6.7)
Surgery optimal debulking (< 1 cm)	23 (60.5)	17 (68)	6 (46.1)
No optimal debulking	3 (7.9)	1 (4)	2 (15.4)
Data unavailable	12 (31.6)	7 (28)	5 (38.5)
Baseline CA 125 value after surgery1
Normal	9 (23.7)	2 (8)	7 (53.8)
Abnormal	15 (39.5)	12 (48)	3 (23)
Not available	14 (36.8)	11 (44)	3 (23)
BRCA 1/2 mutations (all germline)
Positive	7 (18.5)	4 (16)	3 (23.1)
Negative	16 (42.1)	12 (48)	4 (30.8)
Unknown	15 (39.4)	8 (32)	7 (53.8)

¹Baseline CA 125 value: defined as CA 125 value taken on the day of starting adjuvant treatment, intravenous or intraperitoneal, or in the 2 wk period before chemotherapy.

Table 2 Treatment characteristics of intraperitoneal chemotherapy n (%)

Treatment characteristics	Total (n = 38)	Adjuvant group (Group 1, n = 25)	Neoadjuvant group (Group 2, n = 13)
Median	3	3	3
Range	(1-6)	(1-6)	(1-4)
Completion of IP cycles
1	5 (13.2)	4 (16)	1 (7.7)
2	3 (7.9)	1 (4)	2 (15.3)
3	16 (42.1)	8 (32)	8 (61.5)
4	9 (23.7)	8 (32)	1 (7.7)
5	1 (2.6)	1 (4)	0 (0)
6	4 (10.5)	3 (12)	1 (7.7)
IP cisplatin
Starting dose 75 mg/m2	35 (92.1)	24 (96)	11 (84.6)
Dose reduction to 60 mg/m2	11 (28.9)	6 (24)	5 (38.5)
IP paclitaxel
Dose reduction	2 (5.3)	2 (8)	0/13 (0)
Dose omission	20 (52.6)	11 (44)	9 (69.2)
Changed to IV abraxane	3 (7.9)	1 (4)	2 (15.4)
Treatment delay
Delay in starting a new cycle	8 (21.1)	5 (20)	3 (23.1)
Delay in day 8 treatment	8 (21.1)	5 (20)	3 (23.1)
Prophylactic hydration planned	10 (26.3)	7 (18.4)	3 (21.1)

IP: Intraperitoneal.

Table 3 Treatment regimen variations in the intraperitoneal therapy, either in the neoadjuvant or adjuvant n (%)

Treatment regimens	Total, n = 38	Adjuvant group, n = 25	Neoadjuvant group, n = 13
Taxol 175 mg/m2, Carboplatin AUC 5 or 6 every 3 wk	21 (55.3)	14 (56)	7 (54)
Carboplatin AUC 5 or 6, Taxol 80 mg/m2 day 1, 8, 15 every 3 wk (dose dense)	3 (7.9)	2 (8)	1 (8)1
Taxol 80 mg/m2 day 1, 8, Carboplatin AUC 2 day 1, 8 every 3 wk (weekly regimen)	1 (2.6)	0 (0)	1 (8)
Carboplatin AUC 5 and Docetaxel 75 mg/m2 every 3 wk	2 (5.2)	1 (4)	1 (8)
Carboplatin AUC 5 Gemcitabine 800 mg/m2 day 1, 8 every 3 wk (due to peripheral neuropathy)	1 (2.6)	1 (4)	0 (0)
Carboplatin AUC 5 or 6, Abraxane D1, 8 every 3 wk (due to allergic reaction to Taxel)	3 (7.9)	1 (4)	2 (15)
Carboplatin AUC with Taxol x1, with Docetaxel x1 and with Gemcitabine x1 (due to allergic reaction)	1 (2.6)	1 (4)	0 (0)
No IV treatment, IP treatment only	6 (15.8)	5 (20)	1 (8)
Completion of ≥ 6 cycles of IV + IP treatment	34 (89.5)	22 (88)	12 (92)
Completion of 7-10 cycles of IV + IP	5 (13.1)	2 (8)	3 (23)
Subsequent treatment with Bevacizumab at progression	19 (50)	13 (52)	6 (46)

¹This patient also received Bevacizumab with dose dense regimen in the neoadjuvant period. IP: Intraperitoneal; IV: Intravenous.

Table 4 Safety profile and side effects (grade 3 or 4) n (%)

Toxicities	Adjuvant group, n = 25 (100)	Neoadjuvant group, n = 13 (100)
Abdominal pain/pelvic pain	16 (64)	5 (38.5)
Nausea/vomiting	9 (36)	4 (30.8)
Fatigue	2 (8)	2 (15.4)
Renal insufficiency	0 (0)	3 (23.1)
Dehydration/hypotension	4 (16)	2 (15.4)
Catheter malfunction/infection	1 (4)	0 (0)
Anemia	3 (12)	1 (7.7)
Thrombocytopenia	1 (4)	0 (0)
Neutropenia	5 (20)	1 (7.7)
Hypokalemia	1 (4)	4 (30.8)
Hypomagnesemia	3 (12)	2 (15.4)

Table 5 The characteristics of patients with BRCA germline mutations

Serial Number	Age at diagnosis (yr)	BRCA mutation	Significance	Group assignment	PFS per study (mo)	PFS1	Recurrence
3	50	BRCA 1, Q1395X (4302C>T)	Deleterious	1	51.2+	73.2+	No
4	52	BRCA 1, 187del AG	Deleterious	1	15.5		Yes
7	58	BRCA 1, Q310X	Deleterious	1	14+	36+	No
22	56	BRCA 1, G1706E	Suspected deleterious	1	23.5		Yes, deceased
23	54	BRCA 1, unknown	Deleterious	1	12.9		Yes
28	41	BRCA 1, C64G (309T>G)	Deleterious	2	35.7+	53	Splenic recurrence, at 53 mo
35	40	BRCA 1, 187delAG	Deleterious	2	29.9+	51.9+	No

¹Progression free survival (PFS) used the cut of day of 1/30/2019. PFS per study used cut off day of March 30, 2017. PFS: Progression free survival.