A phase I study of the oral platinum agent satraplatin in sequential combination with capecitabine in the treatment of patients with advanced solid malignancies

Figures & data

Table I. Patient characteristics.

	Dose escalation*	Recommended dose**
No. of treated patients	17	20
Median age (range)	68 (35–78)	67 (56–77)
Male/Female	12/5	13/7
ECOG PS 0/1/2	9/7/1	11/9/0
Tumor type
Prostate	8	11
Ovarian	2	5
Others	7	4
Prior cancer treatments
Radiotherapy	13	10
Chemotherapy	17	20
No. of chemotherapy lines for advanced disease
0	1^a	1^b
1	11	13
2	5	6
Prior platinum	7	6
Prior fluoropyrimidine	4	0

Legend: RD, recommended dose; ECOG PS, Eastern Cooperative Oncology Group Performance Status.

*Patients enrolled in the Dose Escalation Phase of the study, excluding seven patients treated at the Recommended Dose of S 70/C 2000.

**All patients treated at the Recommended Dose, including seven patients enrolled in the Dose Escalation Phase and 13 patients enrolled in the RD Expansion Phase.

^aOne patient with metastatic pancreatic cancer received the study treatment as first line.

^bOne patient received only adjuvant chemotherapy.

Table II. Number of patients and DLTs per dose level.

	Dose level S (mg/m^2/day)/C (mg/m^2/day)	Number of evaluable/treated patients	Number of patients with DLT	DLT description
Dose Escalation Phase	S 60/C 1650	6/7*	0	None
	S 80/C 1650	6/6	2	• Thrombocytopenia maximum G3 with > 4 dosing days of C skipped • Thrombocytopenia G4 with hemorrhage
	S 60/C 2000	3/4**	0	None
	S 70/C 2000 MTD/RD	6/7^a	1	• Nausea G3 and lack of recovery by day 42 of neutropenia G2
RD Expansion Phase	S 70/C 2000	12/13^b	1	• > 4 doising days of C skipped for G2 nausea and vomiting

Legend: S, satraplatin; C, capecitabine; DLT, dose limiting toxicity; G, severity grade by NCI-CTCAE criteria; MTD, maximum tolerated dose; RD, recommended dose.

*Non drug-related Serious Adverse Event.

**Early occurrence of thrombocytopenia.

^aNo patient's compliance.

^bPatient's decision to withdraw the study.

Table III. Hematological toxicity by patient.

		Cycle 1					All cycles
Parameter and dose level S (mg/m^2/day)/C (mg/m^2/day)	Patients n	G1 n	G2 n	G3 n	G4 n	All grades (%) n(%)	1 n	2 n	3 n	4 n	All grades (%) n(%)
Thrombocytopenia
Any dose level	37	15	5	2	1	23 (62.2%)	17	10	3	1	31 (83.8%)
S 60/C 1650	7	4	0	0	0	4 (57.1%)	5	0	0	0	5 (71.4%)
S 80/C 1650	6	1	1	2	1	5 (83.3%)	0	2	3	1	6 (100.0%)
S 60/C 2000	4	1	1	0	0	2 (50.0%)	2	1	0	0	3 (75.0%)
S 70/C 2000	20	9	3	0	0	12 (60.0%)	10	7	0	0	17 (85.0%)
Neutropenia
Any dose level	37	4	6	4	0	14 (37.8%)	3	8	5	1	17 (45.9%)
S 60/C 1650	7	2	1	1	0	4 (57.1%)	2	1	1	0	4 (57.1%)
S 80/C 1650	6	0	1	2	0	3 (50.0%)	0	2	2	0	4 (66.7%)
S 60/C 2000	4	2	1	0	0	3 (75.0%)	1	2	0	0	3 (75.0%)
S 70/C 2000	20	0	3	1	0	4 (20.0%)	0	3	2	1	6 (30.0%)

Legend: S, satraplatin; C, capecitabine; n (%), number of patients (percentages based on the number of treated patients); G, severity grade by NCI-CTCAE criteria.

Table IV. Common (incidence ≥10%) and severe non-hematological toxicities.

	Dose escalation*		Recommended dose**
	All grades		G3		All grades
Adverse event	n	%	n	%	n	%
Nausea	10	58.8	2	10.0	11	55.0
Fatigue	7	41.2	1	5.0	7	35.0
Anorexia	7	41.2			7	35.0
Diarrhea	6	35.3			13	65.0
Vomiting	6	35.3	1	5.0	8	40.0
Asthenia	2	11.8			4	20.0
Peripheral sensory neuropathy	2	11.8			1	5.0

Legend: RD, recommended dose; n (%), number of patients (percentages based on the number of treated patients); G, severity grade by NCI-CTCAE criteria.

*Patients enrolled in the Dose Escalation Phase of the study, excluding seven patients treated at the Recommended Dose of S 70/C 2000.

**All patients treated at the Recommended Dose, including seven patients enrolled in the Dose Escalation Phase and 13 patients enrolled in the RD Expansion Phase.

Figure 1. Treatment modifications at S 70/C 2000 (RD) and S 80/C 1650. A) Patients with at least one S (± C) Dose Reduction. B) Cycles administered at Reduced S (± C) Dose and Delayed for Toxicity.

Table

Site	EC registration number for the study	EC approval date
Istituto Oncologico della Svizzera Italiana, Bellinzona	1745	Jan 24, 2006
Centre Pluridisciplinaire d'Oncologie, Lausanne	58/06	Mar 13, 2006
Kantonsspital St. Gallen, St. Gallen	EKSG 06/028 SG 266/06	Jun 2, 2006
Universitätsspital Basel, Basel	114/06	Jun 2, 2006