Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site

Figures & data

Table I. Patient characteristics (second-line therapy – capecitabine and oxaliplatin).

Pt	Sex/Age	PS	Histology and pathological suggestion of primary site	No of metastatic sites	Best response	OS (months)	Further treatment at progression
1.	M/40	1	Adenoc; Upper GI	>2	PD	2.9	No
2.	F/57	2	Adenoc; Upper GI	2	PD	2.0	No
3.	M/55	2	Adenoc; Upper GI	1 (peritoneum)	PD	1.7	No
4.	F/66	0	Adenoc; Upper GI	1 (lymph nodes)	PD	13.6	Gimatecan (4 cycles)
5.	M/66	1	Adenoc; Pancreas or bile duct	2	PD	2.9	No
6.	F/51	1	Adenoc; Pancreas or bile duct	>2	-	1.5	No
7.	F/52	1	Adenoc; Upper or lower GI	1 (lymph nodes)	SD	15.3	PL G (2 cycles); G (2 cycles)
8.	M/46	0	Adenoc; Upper or lower GI	1 (lymph nodes)	PR	32.9	After CAOx, RT (2 GY×30) on residual tumor. At PD Recentin (4 cycles)
9.	M/51	2	Adenoc; Colon/rectum	2	-	0.5	No
10.	F/32	1	Adenoc; Colon/rectum	1 (liver)	PD	2.0	No
11.	M/61	1	Adenoc; Colon/rectum	>2	SD	4.1	No
12.	F/49	1	Carc; Pancreas or internal genitalia	>2	PD	2.8	No
13.	M/51	2	Adenoc; Lung or upper GI	>2	PD	0.9	No
14.	F/62	2	Adenoc; Breast or pancreas	>2	PD	5.6	No
15.	F/33	0	Adenoc; Breast or upper GI	1 (liver)	PR	33.7	Intrahepatic arterial FMI; chemoembolization with A; BVER (1 cycle); ER(4 cycles)
16.	M/58	1	Carc; Salivary gland, esophagus or lung	>2	SD	3.9	No
17.	M/64	0	Adenoc; Upper GI, colon, urothelial	1 (peritoneum)	SD	16.3	^+ CBEVC
18.	M/45	0	Carc; Lung or pancreas	>2	PD	6.3	No
19.	F/55	0	Adenoc; Upper GI or ovary	>2	PD	7.7	No
20.	M/63	1	Carc; Kidney or urothelial	>2	PD	2.1	No
21.	F/43	1	Carc; Lung, breast or internal genitalia	>2	SD	15.9	^++CBMVB(5 cycles);PXDCBPL(4 cycles)
22.	M/47	0	Carc; No Suggestion	1 (liver)	PR	52.7	CBPLG (8 cycles); PXDCBPL(32 cycles)
23.	F/55	1	Carc; No Suggestion	>2	-	2.5	No
24.	M/39	1	Carc; No Suggestion	2	PD	12.2	^+++ Gimatecan (2 cycles); SR(8 weeks)
25.	F/61	1	Squam. carc; No Suggestion	>2	PD	3.7	No

Pt: patient number; PS: Performance Status; Adenoc: adenocarcinoma; Carc: carcinoma; Squam. carc: squamous cell carcinoma; GI: gastrointestinal;

⁺Identification of primary tumour in coecum. Histology: goblet cell carcinoid.

⁺⁺Identification of primary tumour in the renal pelvis.

⁺⁺⁺Identification of primary tumour in kidney.

P_L: paclitaxel; G: gemcitabine; C_A: capecitabine; O_x: oxaliplatin; RT: radiotherapy; F: 5-fluororacil; M;: mitomycin; A: adriamycin; B_v: bevacizumab; E_R: erlotinib; C_B: carboplatin; E: etoposid; V_c: vincristin; M: methotrexate; V_B: vinblastin; P_XD: berlinostat; S_R: sorafenib.

Figure 1. Kaplan-Meier curves for progression-free survival (broken line) and overall survival (continous line) (n = 25). Median PFS was 2.3 months (95% CI: 1.8–2.8) and median OS was 3.9 months (95% CI: 1.9–5.9).

Table II. Treatment-related toxicities* (No of cycles = 99) - rates in brackets.

	All grades	Grade 1	Grade 2	Grade 3	Grade 4
Hematological toxicity
Anemia	53 (53.6)	36 (36.4)	17 (17.2)	0	0
Thrombocytopnia	65 (65,6)	53 (53.5)	8 (8.1)	3 (3.0)	1 (1.0)
Neutropenia	9 (9.1)	5 (5.1)	3 (3.0)	0	1 (1.0)
Febrile neutropenia					1 (1.0)
Non-hematological toxicity
Nausea	50 (50.4)	34 (34.3)	14 (14.1)	2 (2.0)	0
Vomiting	18 (18.2)	7 (7.1)	9 (9.1)	2 (2.0)	0
Diarrhoea	16 (16.2)	10 (10.1)	5 (5.1)	1 (1.0)	0
Hand-foot syndrome	9 (9.1)	5 (5.1)	4 (4.0)	0	0
Mucositis	5 (5.0)	4 (4.0)	1 (1.0)	0	0
Fatigue	60 (60.5)	43 (43.4)	13 (13.1)	4 (4.0)	0

*According to Common Terminology Criteria for Adverse Events (CTCAE) v 3.0.

Table III. Second-line chemotherapy regimens in CUP patients.

Regimens	Number of patients	Response rate (%)	Mediän Survival (months)	The 1-year and 2-year survival (%)	Reference
G	39	8	NR	NR	Hainsworth et al., 2001 [7]
F + leucoverin	25	0	3	NR	Culine et al., 2001 [6]
GDX	15	28.6	8	NR	Pouessel et al., 2003 [9]
GIR	40	10^a	4.5	25 and 13	Hainsworth et al., 2005 [8]
Mean	119 (total)	11.7	5.2

G: gemcitabine, F: 5-fluororacil; D_x: docetaxel, I_R: irinotecan, NR: not reported.

^aResponse rate calculated by intention-to treat analysis.

Hainsworth JD, Burris HA, III, Calvert SW, Willcutt NT, Scullin DC, Jr., Bramham J, . Gemcitabine in the second-line therapy of patients with carcinoma of unknown primary site: A phase II trial of the Minnie Pearl Cancer Research Network. Cancer Invest 2001;19:335–9.

 PubMed Web of Science ®Google Scholar

Culine S, Ychou M, Fabbro M, Romieu G, Cupissol D. 5-fluorouracil and leucovorin as second-line chemotherapy in carcinomas of unknown primary site. Anticancer Res 2001;21:1455–7.

 PubMed Web of Science ®Google Scholar

Pouessel D, Culine S, Becht C, Romieu G, Fabbro M, Ychou M, . Gemcitabine and docetaxel after failure of cisplatin-based chemotherapy in patients with carcinoma of unknown primary site. Anticancer Res 2003;23:2801–4.

 PubMed Web of Science ®Google Scholar

Hainsworth JD, Spigel DR, Raefsky EL, Kuzur ME, Yost K, Kommor M, . Combination chemotherapy with gemcitabine and irinotecan in patients with previously treated carcinoma of an unknown primary site: A Minnie Pearl Cancer Research Network Phase II trial. Cancer 2005;104:1992–7.

 PubMed Web of Science ®Google Scholar