Table 2.
Failure of early non-precision clinical trials for RAS inhibitors or farnesyl transferase inhibitors (FTIs) involving HNSCC patients.
| Clinical trial ID | Clinical trial (tumor type; N) | Target(s) | Drug(s) | No. of HNSCC patients | HNSCC patient outcome | Outcomes of non-HNSCC patients | Ref |
|---|---|---|---|---|---|---|---|
| N.A. | Phase I (HNSCC and NSCLC; N = 9) | FT/GGTase-I | L-778,123 [with standard radiotherapy] | 3 | 2 had complete clinical respones with no evidence of disease at follow-up examinations, but MTD of th L-778,123/radiation combination was not well-defined. | Of the 4 evaluable NSCLC patients, 3 had a complete response and 1 had a partial response. | 41 |
| NCT00003430 | Phase I (HNSCC and unspecified solid tumors; N = N.A.) | FT/GGTase-I | L-778,123 | N.A. | “Completed” but results unavailable. | N.A. | N.A. |
| NCT00006242 | Phase I (multiple solid tumors; N = 44) | FT | BMS-214662 | 2 | No objective responses reported. | Antitumor activity was observed in 1 h I.V. infusion in patients. A pancreatic cancer patient has prolonged stable disease for more than five years under BMS-214662 treatment; A NSCLC patient has 40% size reduction in liver metastasis and complete shrinkage in one of three brain metastases. | 42 |
| NCT00005973 | Phase I (multiple solid tumors; N = 30) | FT | BMS-214662 | 6 | No objective responses reported. | A minor response in a NSCLC patient; A weekly 1 h infusion did not provide sustained and substantial enough FTase inhibition for apoptosis. | 43 |
| NCT00038584 | Phase Ib (HNSCC; N = 37) | FT | Lonafarnib | 37 | “Clinical responses” were seen at all lonafarnib dose levels (oral 100 mg twice daily (b.i.d.), 200 mg b.i.d., or 300 mg b.i.d. for 8 to 14 days before surgical resection), with marked tumor reduction in 4 of 22 evaluable patients. 3 of 17 treated patients demonstrated partial responses. | N.A. | 44 |
| NCT00073450 | Phase II (HNSCC; N = 15) | FT | Lonafarnib | 15 | 7 patients (47%) had stable disease; Well-tolerated but no objective responses observed in the first 15 patients enrolled, and the study is terminated to further accrual. | N.A. | 45 |
| NCT00102635 | Phase I (HNSCC; N = N.A.) | FT | Lonafarnib [with 4-HPR] | N.A. | Terminated due to slow accrual. | N.A. | N.A. |