The combination of sunitinib (50 mg daily for 4 out of 6 weeks or 37.5 mg daily as a continuous dose) and tremelimumab (6, 10, or 15 mg kg−1) produced unexpected and severe renal toxicity in a phase I trial in patients with metastatic renal cancer; notably, renal toxicity is not a limiting toxicity of either agent alone (Rini et al, 2011).
Nephrotoxicity and gastrointestinal toxicity often limits the clinical use of antitumour agents such as CDDP, but 254-S causes less nephrotoxicity and gastrointestinal toxicity than CDDP, although its haematological toxicity can be a limiting factor at high dosage, as found with CBDCA (Kameyama et al, 1990; Ota et al, 1992; Suzumura et al, 1989).
The effect of gemcitabine on transaminases is well described and is a dose limiting toxicity at higher doses of gemcitabine (Fossella et al, 1997).
Kidney toxicity is a limiting factor for radionuclide therapy with somatostatin analogs, especially when using 90Y [4, 14, 20].
Toxicity has been a limiting factor in clinical pancreatic cancer treatment: combined therapy with cisplatin and gemcitabine has shown promising results in phase II and III trials, but it was followed by severe toxicity and therefore has not been approved as a standard of care [ 4].
Severe mucositis (World Health Organization [WHO]) grade 3 to 4 was the limiting toxicity and was seen in 79% of patients.
Neutropenia was the dose limiting toxicity for both groups.
There was no dose limiting toxicity identified in this study.
However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients.
The primary endpoint is the occurrence of a dose limiting toxicity defined as any Grade IV toxicity according to CTCAE Version 4.0, possibly, probably or definitely associated to study treatment and occurring during 30 days after completion of the study treatment.
