Limits...
A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours.

Boven E, Massard C, Armand JP, Tillier C, Hartog V, Brega NM, Countouriotis AM, Ruiz-Garcia A, Soria JC - Br. J. Cancer (2010)

Bottom Line: In a second cohort, the sunitinib dose was reduced to 25 mg per day.Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions.Therefore, this particular combination will not be pursued for further studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam NL-1081 HV, The Netherlands. e.boven@vumc.nl

ABSTRACT

Background: Sunitinib is a multitargeted, oral tyrosine kinase inhibitor with antitumour and antiangiogenic activity. We investigated the safety and pharmacokinetics of sunitinib in combination with irinotecan in patients with advanced, refractory solid tumours.

Methods: Sunitinib was initially administered once daily at 37.5 mg per day on days 1-14 of a 21-day cycle, in which irinotecan 250 mg m(-2) was given on day 1. In a second cohort, the sunitinib dose was reduced to 25 mg per day. Blood samples were collected for pharmacokinetic studies.

Results: In the sunitinib 37.5 mg per day cohort, 3 out of 10 evaluable patients had objective responses, but dose-limiting toxicities (DLTs) of neutropenia, pneumococcal sepsis, and fatigue were observed. There were no DLTs in the sunitinib 25 mg per day cohort. Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions. The maximum tolerated dose was defined as sunitinib 25 mg per day (days 1-14) with irinotecan 250 mg m(-2) (day 1), but no activity was observed at this dose.

Conclusion: Although a higher sunitinib dose of 37.5 mg per day (days 1-14) with irinotecan showed preliminary evidence of antitumour activity, this dose was poorly tolerated. Therefore, this particular combination will not be pursued for further studies.

Show MeSH

Related in: MedlinePlus

Partial response in a patient with inoperable non-small-cell lung cancer receiving sunitinib 37.5 mg per day and irinotecan. CT scans are shown at baseline (A), after 7 weeks (B) and 6 months (C) on treatment.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2965864&req=5

fig1: Partial response in a patient with inoperable non-small-cell lung cancer receiving sunitinib 37.5 mg per day and irinotecan. CT scans are shown at baseline (A), after 7 weeks (B) and 6 months (C) on treatment.

Mentions: The majority of patients (10 out of 11 patients in the sunitinib 37.5 mg per day group and all 10 patients in the 25 mg per day group) had measurable disease at baseline, and were available for assessment of tumour response (Table 4). Out of 10 evaluable patients, 3 (30%) in cohort 1 had a confirmed partial response: one patient with submandibular cancer, one patient with oropharyngeal cancer who experienced complete regression of the target lesion in the presence of persisting non-target lesions, and one patient with relapsed NSCLC. Figure 1 shows durable tumour shrinkage in the patient with NSCLC. A further two patients in cohort 1 experienced stable disease for ⩾12 weeks (one patient each with CRC and leiomyosarcoma). In cohort 2, two patients (one patient each with prostate cancer and cervical cancer) had a best response of stable disease for ⩾12 weeks. Tumour response assessments (percentage change from baseline in sum of target lesions) are shown for individual patients in Figure 2.


A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours.

Boven E, Massard C, Armand JP, Tillier C, Hartog V, Brega NM, Countouriotis AM, Ruiz-Garcia A, Soria JC - Br. J. Cancer (2010)

Partial response in a patient with inoperable non-small-cell lung cancer receiving sunitinib 37.5 mg per day and irinotecan. CT scans are shown at baseline (A), after 7 weeks (B) and 6 months (C) on treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965864&req=5

fig1: Partial response in a patient with inoperable non-small-cell lung cancer receiving sunitinib 37.5 mg per day and irinotecan. CT scans are shown at baseline (A), after 7 weeks (B) and 6 months (C) on treatment.
Mentions: The majority of patients (10 out of 11 patients in the sunitinib 37.5 mg per day group and all 10 patients in the 25 mg per day group) had measurable disease at baseline, and were available for assessment of tumour response (Table 4). Out of 10 evaluable patients, 3 (30%) in cohort 1 had a confirmed partial response: one patient with submandibular cancer, one patient with oropharyngeal cancer who experienced complete regression of the target lesion in the presence of persisting non-target lesions, and one patient with relapsed NSCLC. Figure 1 shows durable tumour shrinkage in the patient with NSCLC. A further two patients in cohort 1 experienced stable disease for ⩾12 weeks (one patient each with CRC and leiomyosarcoma). In cohort 2, two patients (one patient each with prostate cancer and cervical cancer) had a best response of stable disease for ⩾12 weeks. Tumour response assessments (percentage change from baseline in sum of target lesions) are shown for individual patients in Figure 2.

Bottom Line: In a second cohort, the sunitinib dose was reduced to 25 mg per day.Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions.Therefore, this particular combination will not be pursued for further studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam NL-1081 HV, The Netherlands. e.boven@vumc.nl

ABSTRACT

Background: Sunitinib is a multitargeted, oral tyrosine kinase inhibitor with antitumour and antiangiogenic activity. We investigated the safety and pharmacokinetics of sunitinib in combination with irinotecan in patients with advanced, refractory solid tumours.

Methods: Sunitinib was initially administered once daily at 37.5 mg per day on days 1-14 of a 21-day cycle, in which irinotecan 250 mg m(-2) was given on day 1. In a second cohort, the sunitinib dose was reduced to 25 mg per day. Blood samples were collected for pharmacokinetic studies.

Results: In the sunitinib 37.5 mg per day cohort, 3 out of 10 evaluable patients had objective responses, but dose-limiting toxicities (DLTs) of neutropenia, pneumococcal sepsis, and fatigue were observed. There were no DLTs in the sunitinib 25 mg per day cohort. Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions. The maximum tolerated dose was defined as sunitinib 25 mg per day (days 1-14) with irinotecan 250 mg m(-2) (day 1), but no activity was observed at this dose.

Conclusion: Although a higher sunitinib dose of 37.5 mg per day (days 1-14) with irinotecan showed preliminary evidence of antitumour activity, this dose was poorly tolerated. Therefore, this particular combination will not be pursued for further studies.

Show MeSH
Related in: MedlinePlus