| General information |
| Database: | DB00398 |
| Objective: | Thisphase I study determined the maximaltolerated dose, doselimiting toxicities, pharmacokinetics, and recommended dose of erlotinib with docetaxel. |
| Authors: | Kraut EH, et al |
| Title: | Phase I and pharmacokinetic study of erlotinib (OSI774) in combination with docetaxel in squamous cell carcinoma of the head and neck (SSCHN). |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2011 |
| PMID: | 20490801 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | erlotinib (OSI774) + docetaxel |
| Study Type: | Phase I and pharmacokinetic study |
| Key Patients Feature: | Patients eligible for this trial had pathologically confirmed recurrent or metastatic squamouscell carcinoma of the head and neck or locally advanced disease not felt curable by radiationand surgery; bidimensionally measurable disease; ECOG performance status of 0-2; age more than and equal to 18; peripheral neuropathy less than and equal to grade 2; neutrophil counts more than and equal to 1, 500/¦ÌL, platelets more than and equal to 100, 000 ¦ÌL, normal creatinine; SGPT and SGOT less than and equal to 2¦Ìl. patients were allowed one chemotherapy inadjuvant or neoadjuvant setting and one chemotherapy for metastatic disease. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were orally given erlotinib (50 mg) daily plus 35 mg/m2 of docetaxel intravenously weekly ¡Á 3 every 4 weeks. Dose escalation of erlotinib was in 50mg increments until toxicity.Pharmacokinetics were studied with LCMS/MS, standard, and population pharmacokinetic methods. |
| Primary End Point: | the doselimiting toxicity and MTD; |
| Secondary End Point: | the pharmacokinetics |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | The most frequentside effects were diarrhea, fatigue, skin rash, anemia, and hypoalbuminemia.the recommendedphase II dose of erlotinib 50 mg and docetaxel 35mg/m2, |
| Objective Response Rate: | three patients had stable disease and three patients showed disease progression. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent side effects were diarrhea, fatigue, skin rash, anemia, and hypoalbuminemia. |
| Conclusions: | The combination of erlotinib and docetaxel was associated with significant toxicity, which limited the amount of administered erlotinib. Dosing forphase II trials was docetaxel 35 mgm2 and erlotinib 50 mg. The reason for excessive toxicity is not clear, but not due to change in pharmacokinetics. |