Table 2.
Dose levels and patient treatment with lonafarnib, gemcitabine and cisplatin
| Cohort 1 (heavily pre-treated) dose levels |
Lonafarniba | Gemcitabineb | Cisplatinc | Number of Patients (# of courses) |
Patients with dose limiting toxicity (n) |
|---|---|---|---|---|---|
| −1 | 50 | 750 | 75 | None | |
| 1 | 75 | 750 | 75 | 3 (7) | None |
| 2 | 75 | 1,000 | 75 | 7 (14) | Grade 4 neutropenia and grade 4 thrombocytopenia (1) |
| Grade 4 neutropenia/neutropenic fever (1) | |||||
| 3 | 100 | 1,000 | 75 | 4 (7) | Grade 4 neutropenia, grade 4 thrombocytopenia grade 4 diarrhea (1) |
| Cohort 2 (less heavily pre-treated) dose levels | |||||
| 6 | 75 | 1,000 | 75 | 3 (16) | Grade 4 neutropenia and platelets (1) |
| Grade 4 neutropenia with fever, grade 4 platelets, grade 3 atigue (1) |
|||||
| Cohort 3 (less heavily pre-treated) dose levels | |||||
| 10 | 75 | 750 | 75 | 2 (4) | None |
| 11 | 100 | 1,000 | 75 | 3 (5) | None |
a
Lonafarnib dose in mg BID on days 2–28 cycle 1 and days 1–28 subsequent cycles in cohort 1, days 8–28 of cycle 1 and days 1–28 of subsequent 28-day cycles in cohort 2, and on days 8–21 of cycle 1 and days 1–21 to of subsequent 21-day cycles in cohort 3, due to nausea and vomiting noted with gemcitabine and cisplatin administration
b
Gemcitabine dose in mg/m2 on days 1, 8, 15 q 28 days in cohorts 1 and 2 and on days 1 and 8 q 21 days in cohort 3
c
Cisplatin dose in mg/m2 on day 1 of each cycle