A search of the literature did not find strong evidence to support the use of concurrent cisplatin (weekly) chemoradiation in the treatment of muscle invasive bladder cancer. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by Gogna et al.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase III trials |
Coppin et al 1996r |
Yes |
No |
100 mg/m2 2 weekly |
Phase II trials |
Gogna et al 2006r
|
Yes |
Yes |
|
Case series |
Efstathiou et al 2012r |
Yes |
No |
Cisplatin based |
|
Rodel et al 2002r |
Yes |
No |
Cisplatin based |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
2012 |
Yes |
Not specified |
- |
BCCA |
2011 |
Yes |
No |
40 mg/m2 |
CCO |
- |
- |
- |
- |
Two phase 2 trials conducted by TROG for patients with localised (T2-4a) muscle-invasive bladder cancer examined the feasibility, toxicity and efficacy of radiation therapy in combination with cisplatin 35 mg/m2 weekly.r 113 patients were enrolled 6 cycles of cisplatin with radiation therapy 64Gy over 6.5 weeks (TROG 99.06) was better tolerated than 7 cycles of cisplatin with radiation therapy 63 Gy over 7 weeks (TROG 97.01). The dose-intensity of cisplatin in this protocol is taken from the TROG 99.06 trial, and has not been tested in a phase 3 trial.r
Cisplatin is used for many cancers as a radiosensitiser. Strongest evidence for use of cisplatin as a radiosensitiser during radiation therapy for muscle-invasive bladder comes from a phase 3 trial conducted by the National Cancer Institute of Canada Clinical Trials Group for patients with T2 to T4b disease selected for either definitive radiation therapy or radiation therapy followed by cystectomy. 99 patients were randomised to receive radiation therapy with or without cisplatin 100 mg/m2 2-weekly for 3 cycles. The chemoradiation therapy group had a lower rate of pelvic relapse (40% vs 59% at 5 years, p=0.38) but the trial was underpowered to demonstrated any potential effect on overall survival. All 3 planned cycles of chemotherapy were delivered to 78% of patients in the chemotherapy group. There are no other randomised trials in this setting comparing radiation therapy with or without concurrent cisplatin.r
Two large case series from Massachusetts General Hospital, Boston, USA (n=348)r and University of Erlangen, Germany (n=289)r report the use of radiation therapy with concurrent cisplatin-based chemotherapy after maximal transurethral resection of bladder tumour. The dosing and scheduling of cisplatin during radiation therapy was highly variable: eg. 100 mg/m2 3-weekly, 70 mg/m2 3-weekly, multi-day cisplatin each week, cisplatin alone in combination with other agents, with/ without neoadjuvant or adjuvant chemotherapy.
The dose and scheduling of cisplatin used in this protocol were chosen because of concerns about deliverability of high-dose intermittent cisplatin during radiation therapy for invasive bladder cancer, and adapted from the dose and scheduling cisplatin used in randomised trial of radiation therapy alone or in combination with weekly cisplatin 40mg/m2 for bulky stage 1B cervical cancer.r Link to Cervical Locally Advanced SCC Cisplatin Chemoradiation
Efficacy
In TROG 97.01 and 99.06 trials, initial response of the primary tumour at 6 months was assessed by cystoscopy as follows: complete response (CR) in 70%, persistent or progressive disease in 19%, superficial TCC in 4% and was unknown due to early death in 7%. Local invasive recurrence occurred in 14% of patients who were in CR at 6 months. The local control rate at 5 years was 45% with a functional bladder being retained in 61%. Relapse-free survival and disease-specific survival at 5 years were 33% and 50% respectively.r
© Radiotherapy and Oncology 2006
Toxicity
In TROG 97.01 and 99.06 trials grade 3/4 toxicity by combined RTOG/EORTC criteria were as follows: acute urinary toxicity occurred in 23%, acute cisplatin-related toxicities in 33% with 12% requiring significant dose modification, late bladder toxicity in 4%, late bowel toxicity in 2%.r
© Radiotherapy and Oncology 2006