1. The treatment of metastatic squamous cell carcinoma (SCCA) of the anal canal: A single institution experience P. Pathak, B. King, A. Ohinata, P. Das, C.H. Crane, J.L. Chase, C. Eng The University of Texas M. D. Anderson Cancer Center, Houston, Texas

2. Objectives To evaluate progression-free survival (PFS) following first- line therapy in metastatic SCCA of the anal canal. To evaluate overall survival (OS) from time of diagnosis to death or point of last follow up in patients who received first- line therapy.

3. Methods Study Design and Population Single institution, retrospective chart review. Patients with histologically confirmed stage IV squamous cell carcinoma of the anal canal (SCCA) between January 2000 to January 2007. Inclusion Criteria Stage IV SCCA of the anal canal who have received first- line therapy based on pathology, radiology reports and have had follow up at M.D. Anderson Cancer Center. Exclusion Criteria Patients with anal cancer of any other histology other than squamous cell type. Patients with prior or concurrent malignancies within the past 5 years excluding superficial skin cancers.

4. Data Collection Patients were identified from electronic medical records. Chart reviews were performed on all patients by at least two investigators. The information collected included: Demographics. Histology and sites of metastasis. Therapy prior to development of metastasis. First-line, second-line, and third-line treatment regimens for metastatic disease

5. Table 1: Patient and Tumor Characteristics Number of Patients 40 Patient Characteristics Median age at diagnosis of metastasis FemalesRace: Caucasians Caucasians African-Americans African-Americans Others OthersHIV+ 56 yrs 75%85%10%5%5% Tumor Characteristics Well differentiated histology Moderately differentiated histology Poorly differentiated histology Liver Metastasis Lung Metastasis Bone Metastasis Distant Lymph Node Metastasis 3%38%43%60%45%20%55%

6. Table 2: Treatment Provided Prior Treatment with Curative Intent: Chemoradiation: 5FU + Mitomycin C 5FU + Mitomycin C Cisplatin Cisplatin Other Other Salvage surgery 73% (29/40) 55% (16/29) 38% (11/29) 7% (2/29) 7% (2/29) 17% (5/29) First-line Therapy for Metastasis: Systemic chemotherapy Systemic chemotherapy + Chemoradiation Systemic Chemotherapy + Biologic Therapy Systemic chemotherapy + Metastatectomy Palliative Chemoradiation Other 55% (22/40) 8% (3/40) 8% (3/40) 3% (1/40) 3% (1/40) 10% (4/40) 12% (5/40) Second-line Therapy : Systemic Chemotherapy Biologic Therapy Surgery 65% (26/40) 65% (26/40) 73% (19/26) 73% (19/26) 15% (4/26) 27% (7/26) 27% (7/26) > 3 Lines of Chemotherapy 43% (16/40) 43% (16/40) Median Follow-up 18 months 18 months

7. Table 3: First-line Chemotherapy Type Patients N=30 (%) 5-FU/capecitabine + Platinum 5-FU/capecitabine + Platinum Irinotecan (CPT-11) + Platinum Irinotecan (CPT-11) + Platinum Taxanes + Platinum Taxanes + Platinum 70% (21/30) 10% (3/30) 20% (6/30)

8. Figure 1: Kaplan-Meier for Progression- Free Survival (N= 37*) * 3 patients are currently receiving chemotherapy

9. Figure 2: Kaplan-Meier for Overall Survival

10. Results There were a total of 53 patients who fulfilled the inclusion criteria; 40 patients were considered evaluable; 6 were lost to follow-up; and 7 were not treated due to poor performance status. A total of 30 out of 40 patients were eligible for response to first-line systemic chemotherapy. The median number of therapies provided = 2. The response rate to first-line systemic chemotherapy was 33%.

11. Conclusions Despite the success of chemoradiation therapy for local disease, an established regimen for the treatment of stage IV patients with squamous cell carcinoma of the anal canal has not been identified. Systemic chemotherapy regimens utilized in more commonly diagnosed squamous cell carcinomas are efficacious in this setting. Consideration of surgery and/or radiation therapy with curative intent for focal metastatic disease is reasonable with multidisciplinary management. Prospective randomized trials of both systemic and biologic therapy in this select group of patients would provide further insight for effective management of this patient population.

12. References 1.Clark MA, Hartley A, Geh JI. Cancer of the anal canal. Lancet Oncol 2004; 5 (3): 149-57. 2.Maggard MA, Beanes, SR, Ko CY. Anal canal cancer: a population-based reappraisal. Dis Colon Rectum 2003; 46 (11): 1517-24.