| General information |
| Database: | DB00554 |
| Objective: | To evaluate the clinicopathological efficacy of neoadjuvant erlotinib (an epidermal growth factor receptor, EGFR, inhibitor) for invasive bladder cancer in patients undergoing radical cystectomy (RC) as despite definitive surgical therapy, only half of patients undergoing RC will have longterm diseasefree survival, and effective adjunctive therapies, especially using agents with lotheyr toxicity, would be a significant advance in the treatment of invasive bladder cancer. |
| Authors: | Pruthi RS, et al |
| Title: | a phase II trial of neoadjuvant erlotinib in patients with muscleinvasive bladder cancer undergoing radical cystectomy: clinical and pathological results. |
| Journal: | BJU Int. |
| Year: | 2010 |
| PMID: | 20089114 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | bladder cancer |
| Cancer Subtype: | muscleinvasive bladder cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II trial |
| Key Patients Feature: | Patients selected for study included thosewith histologically confirmed muscleinvasivebladder cancer (clinical stage T2) who had undergone initial TURBT; these patients weredeemed clinical stage T2 and to be candidatesfor, and had agreed to undergo, conventionaltreatment in the form of RC with curativeintent. Enrolled patients had no evidence oflocally extensive (clinical T3/T4) or metastaticdisease (N+, M+). Eligible patients had normalendorgan function, and no previous historyof treatment with an EGFRI. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | At enrolment, patients had a confirmatoryTURBT and collection of pretreatmentcorrelative tumour tissue. Patients then received 4 weeks of preoperative erlotinib given orally at a daily dose of 150 mg taken with food. Notably, current use ofCYP3A4 inhibitors was specifically excluded in this study. |
| Primary End Point: | the effect on the pathological complete response rate (pT0 rate) |
| Secondary End Point: | the safety |
| Patients Number: | 20 |
| Trial Results |
| DLT_MTD: | The most common treatmentrelated sideeffectwas rash, in 15 patients (75%), ofwhom four (20%) had a rash of NCI grade 3severity in the neoadjuvant course |
| Objective Response Rate: | At a mean followup of24.8 months, 10 patients remain alive andwith no evidence of disease, four withorganconfined disease had progression and nine died, including six from disease andthree from other causes |
| 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 common treatmentrelated sideeffect was rash, in 15 patients (75%), of whom four (20%) had a rash of NCI grade 3 severity in the neoadjuvant course. During the adjuvantphase, six patients (of 12) had a rash, with none being of grade more than and equal to 3. Two patients had complications of chronic cough during the adjuvantphase and in both patients postoperative erlotinib therapy was discontinued. One of these two was diagnosed with interstitial pneumonitis and has not had further pulmonary complications. |
| Conclusions: | The EGFR inhibitor erlotinib, when administered in the neoadjuvant setting, can have beneficial effects in terms of surgical pathology and shortterm clinical outcomes in patients undergoing RC for invasive bladder cancer. Analyses are underway to examine the molecular correlates of the apparent clinical effect of neoadjuvant therapy in these patients. |