Results of the phase I trial of cetuximab with mitomycin c and 5-fluorouracil concurrent with radiotherapy treatment in patients with muscle-invasive bladder cancer.

Authors

Syed Hussain

Syed A. Hussain

University of Liverpool, Clatterbridge Cancer Centre, Liverpool, United Kingdom

Syed A. Hussain , Carey Hendron , Laura Buckley , Lynne Dickinson , Isabel Syndikus , Zafar Malik , Chinnamani Eswar , Nicholas David James

Organizations

University of Liverpool, Clatterbridge Cancer Centre, Liverpool, United Kingdom, CRUK Institute for Cancer Studies, Birmingham, United Kingdom, University of Birmingham, Birmingham, United Kingdom, Clatterbridge Cancer Centre, Wirral, United Kingdom, Clatterbridge Centre for Oncology, Wirral, United Kingdom, Clatterbridge Cancer Centre, Bebington, United Kingdom, Queen Elizabeth Hospital, University of Birmingham, Birmingham, United Kingdom

Research Funding

Other

Background: Synchronous chemo-radiotherapy is an alternative to cystectomy in patients with muscle invasive bladder cancer (MIBC). BC2001 trial reported improved local control in patients randomised to synchronous chemo-radiotherapy compared to radiotherapy alone (James, Hussain, Hall et al NEJM 2012). TUXEDO trial reports phase I trial results with additional weekly cetuximab (Cet) in combination with Mitomycin c (MMC), 5-Fluouracil (5-FU) and concurrent radiotherapy (RT). Methods: This two centre phase I trial recruited 7 patients with MIBC in Queen Elizabeth Hospital Birmingham and Clatterbridge Cancer Centre Liverpool to synchronous chemotherapy using Loading dose of Cet 400 mg/m2 followed by weekly Cet 250 mg/m2, continuous infusion 5-FU 500mg/m2/day during fractions 1-5 and 16-20 of RT and MMC12mg/m2on day 1 in combination with radical RT treatment 64 Gys in 32 fractions. The primary endpoint was to assess toxicity. Secondary end- points included 3 months pathological complete response, loco-regional disease-free survival and overall survival. Results: Median age of patients was 70 (range: 60-75) years, all were male, 6 had received prior neoadjuvant chemotherapy. Two patients had T2B, 3 T3A and 2 T3B disease, all had G3, TCC disease, 6 patients had neo-adjuvant chemotherapy. All 7 patients completed RT as planned except for 1 who withdrew from trial after 5 weeks of protocol treatment due to relocation. Median dose intensity for Cet and MMC was 97.6% and for 5-FU was 99.4%. Grade 3 toxicity to report was maculopapular rash in 3 patients. Grade 2 toxicities include UTI/ frequency/ nocturia / fatigue /constipation / hypokalemia/epistaxis/palmar-plantar reported in 3/1/1/1/1/1/1/2 cases respectively. Grade 2 maculo-papular rash was reported in 3 cases. All seven patients have achieved complete responses at 3 months cystoscopic assessment. Patients continue on surveillance as per TUXEDO trial protocol. Conclusions: Synchronous chemotherapy with Cet and 5FU/MMC concurrent with radical RT is safe to deliver. Complete response rates are encouraging and a phase II trial with added centres within UK is being launched. Clinical trial information: NOT KNOWN.

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Abstract Details

Meeting

2015 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session B: Prostate, Penile, Testicular, and Urethral Cancers, and Urothelial Carcinoma

Track

Urothelial Carcinoma,Prostate Cancer,Penile, Urethral, and Testicular Cancers

Sub Track

Urothelial Carcinoma

Clinical Trial Registration Number

NOT KNOWN

Citation

J Clin Oncol 33, 2015 (suppl 7; abstr 368)

DOI

10.1200/jco.2015.33.7_suppl.368

Abstract #

368

Poster Bd #

H5

Abstract Disclosures

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