Esophageal Cancer abstract, thanks to YMB
Local tumor responses revealed stable disease in nine cases and progressive disease in one case. The overall responses were stable in six and progressive in four cases.
Three patients showed absence of disease upon repeat biopsies.
The above seem to contradict eachother?..what am I missing? As much as we want to see major responses, stable disease in conventional treatment resistant tumors is quite good..esp. in this indication..
Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma
Hideaki Shimada1,5, Hisahiro Matsubara1, Tooru Shiratori1, Takanori Shimizu1, Shinichi Miyazaki1, Shinichi Okazumi1, Yoshihiro Nabeya1, Kiyohiko Shuto1, Hideki Hayashi2, Tooru Tanizawa3, Yukio Nakatani3, Hiromitsu Nakasa4, Mitsukazu Kitada4 and Takenori Ochiai1
We investigated the feasibility, safety, biological activity and therapeutic efficacy of adenovirus-mediated p53 gene transfer in patients with chemoradiation resistant advanced esophageal carcinoma. Eligible patients were not surgical candidates and had measurable, advanced squamous cell carcinoma of the esophagus that was resistant to chemoradiation therapy. On a 28-day cycle, intratumoral injections of Ad5CMV-p53 (INGN 201; ADVEXIN®) were administered on days 1 and 3 at four dose levels (10 × 1011 particles to 25 × 1011 particles) and treated for up to five cycles. Ten patients received a total of 26 cycles with no dose-limiting toxicity. Administration of multiple courses was feasible and well-tolerated. Local tumor responses revealed stable disease in nine cases and progressive disease in one case. The overall responses were stable in six and progressive in four cases. Using polymerase chain reaction (PCR) analyses, gene transfer and p53 specific transgene expression were detected in tumor biopsy tissue from all patients. mRNA levels of p53, p21 and MDM2 increased in all but one case. Three patients showed absence of disease upon repeat biopsies. Substantial improvement in swallowing was observed in one patient with stenotic lesions. Intratumoral injection of Ad5CMV-p53 is safe, feasible and biologically active when administered in multiple doses to patients with esophageal cancer. Observations from this study indicate that this treatment results in local antitumor effects in chemoradiation resistant esophageal squamous cell carcinoma. (Cancer Sci 2006; 97)<< |
