Assessment of the radiation-equivalent of chemotherapy contributions in 1-phase radio-chemotherapy treatment of muscle-invasive bladder cancer.
OBJECTIVE
To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer.


METHODS
A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered.


RESULTS
The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy.


CONCLUSIONS
Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.
Department of Oncology, Queens Hospital, London, United Kingdom. Electronic address: george.plataniotis@nhs.net.
George A
GA
Plataniotis
Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom.
Roger G
RG
Dale
D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D017321:Clinical Trials, Phase I as Topic; D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D060828:Induction Chemotherapy; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D013810:Therapeutic Equivalency; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents