Prostate radiotherapy with carbogen and nicotinamide. Final results of the phase 1b/II PROCON trial
Yip, K. Hoskin, Peter J Thiruthaneeswaran, Niluja Alonzi, R.
Yip, K.
Hoskin, Peter J
Thiruthaneeswaran, Niluja
Alonzi, R.
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Abstract
Purpose or Objective
Prostate tumour hypoxia is associated with resistance to
radiotherapy (RT) and increased likelihood of relapse post
treatment. The concurrent administration of carbogen and
nicotinamide (CON) with RT improves overall survival in
patients with bladder cancer and regional control rates
following laryngeal RT. We evaluated the safety, toxicity
of this approach for patients with high risk prostate
cancer.
Material and Methods
50 patients (with 1 of: T3, Gleason ≥8, PSA ≥20) were
recruited into the single arm phase 1b/II PROCON trial
between Dec 2011 and Sept 2013. They breathed carbogen
via a tight-fitting face mask during RT and took 60mg/kg
of nicotinamide daily prior to the delivery of RT (74Gy/37# to the prostate and 60Gy/37# to the pelvic nodes). Twenty
men also underwent functional MRI imaging; correction of
tumour hypoxia was evaluated by comparing tumour R2*
values before and after carbogen administration. Patients
were assessed during treatment and 2, 4 and 12 weeks
after they had completed RT. The primary endpoints were
prevalence of grade 3 (G3) or worse lower gastrointestinal
(GI) or genitourinary (GU) toxicities during this period.
Secondary end points include PSA progression free survival
(PFS) and overall survival (OS) rates at five years as
calculated by the Kaplan Meier method.
Results
The median duration of follow up was 60 months. All
patients completed the prescribed 37 fraction schedule of
RT over 50 to 56 days (median duration: 52 days). 56%
patients experienced grade 1 nausea (CTCAE v 4.0), and
52% patients received anti-emetic treatment. 22% patients
had a nicotinamide dose adjustment, 20% patients had a
break from nicotinamide and 6% patients discontinued
nicotinamide. 96% patients received carbogen with every
RT fraction. One patient had an interruption of treatment
and received carbogen for 33 of 37 fractions. One patient
discontinued carbogen treatment after 7 fractions. No one
developed G3 or worse lower GI or GU toxicities;
prevalence of G1/G2 toxicities are shown in table 1. The
5 year OS and PSA-PFS rates were 92% and 87%
respectively. Six patients experienced biochemical
progression. Five patients have died but None had
biochemical relapse prior to their death. The functional
MRI analysis showed a mean decrease of 5.8% in tumour
R2* after the application of carbogen, measured in 72 pairs
of pre and post carbogen measurements, indicating that
the carbogen exposure resulted in an immediate
reduction in tumour hypoxia.
Conclusion The prevalence of acute lower GI and GU toxicities among
our cohort, together with their 5 year PSA PFS and OS
rates, are comparable, or superior to, those reported for
patients with high risk prostate cancer receiving RT in
other contemporary trials. The concurrent administration
of CON with RT is safe and effective. It should be further
explored in a phase III setting.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Yip K, Hoskin P, Thiruthaneeswaran N, Alonzi R. PD-0666: Prostate radiotherapy with Carbogen and Nicotinamide. Final results of the phase 1b/II PROCON trial. Radiotherapy and Oncology . 2020 Nov;152:S369–70.