Table 3.
Characteristics of first-in-human phase I clinical trials for recent anticancer agents that were eventually approved by the US FDA*
| Agent | Class or mechanism of action | Year of FDA approval | Dose escalation method | Reason for stopping trial | No. of patients | No. of dose levels | Reference |
| Molecular targeted agents | |||||||
| Trastuzumab | Mab | 1998 | Traditional | PK | 18 | 4 | (11) |
| Imatinib | TKI | 2001 | Traditional | PK | 83 | 14 | (12) |
| Gefitinib | TKI | 2003 | Traditional | Toxicity | 64 | 8 | (13) |
| Erlotinib | TKI | 2004 | Traditional | Toxicity | 40 | 5 | (14) |
| Cetuximab | Mab | 2004 | Traditional | PK | 52 | 6 | (15) |
| Bevacizumab | Mab | 2004 | Traditional | Target inhibition | 25 | 5 | (16) |
| Sorafenib | TKI | 2005 | Traditional | Toxicity | 69 | >5 | (17) |
| Sunitinib | TKI | 2006 | Traditional | Toxicity | 28 | 6 | (18) |
| Panitumumab | Mab | 2006 | Traditional | PK | 96 | 13 | (19) |
| Lapatinib | TKI | 2007 | NR | NR | 81 | NR | (20) |
| Temsirolimus | STKI | 2007 | Modified CRM | Toxicity | 24 | 10 | (21) |
| Cytotoxic agents | |||||||
| Paclitaxel | Anti-tubulin | 1992 | Traditional | Toxicity | 34 | 11 | (22) |
| Vinorelbine | Alkaloid agent | 1994 | Traditional + IPDE | Toxicity | 20 | 7 | (23) |
| Docetaxel | Anti-tubulin | 1996 | ATD | Toxicity | 39 | 6 | (24) |
| Gemcitabine | Antimetabolite | 1996 | Traditional + IPDE | Toxicity | 47 | 12 | (25) |
| Topotecan | Anti–topoisomerase I | 1996 | Traditional | Toxicity | 28 | 5 | (26) |
| Irinotecan | Anti–topoisomerase I | 1998 | Traditional | Toxicity | 17 | 4 | (27) |
| Capecitabine | Antimetabolite | 1998 | Traditional | Toxicity | 34 | 5 | (28) |
| Liposomal doxorubicin | Anti–topoisomerase II | 1999 | Traditional | Toxicity | 26 | 4 | (29) |
| Temozolomide | DNA alkylating | 1999 | Traditional + IPDE | Toxicity | 51 | 15 | (30) |
| Oxaliplatin | DNA alkylating | 2002 | Traditional + IPDE | Toxicity | 23 | 9 | (31) |
| Pemetrexed | Antimetabolite | 2004 | Traditional | Toxicity | 38 | 10 | (32) |
| Trabectedin | Alkaloid agent | 2004 | Traditional | Toxicity | 21 | 4 | (33) |
| Albumin-bound paclitaxel | Anti-tubulin | 2005 | Traditional | Toxicity | 19 | 4 | (34) |
| Ixabepilone | Anti-tubulin | 2007 | ATD | Toxicity | 21 | 4 | (35) |
*
FDA = US Food and Drug Administration; Mab = monoclonal antibody; TKI = tyrosine kinase inhibitor; STKI = serine/threonine kinase inhibitor; NR = not reported; PK = pharmacokinetic data; CRM = continual reassessment method; IPDE = intrapatient dose escalation; ATD = accelerated titration design.