High-dose radiation therapy and neoadjuvant plus concomitant chemotherapy with 5-fluorouracil and cisplatin in patients with locally advanced squamous-cell anal canal cancer: final results of a phase II study.
OBJECTIVE
To analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced anal canal squamous-cell carcinoma (ACC).


METHODS
Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52 T2, 14 T3, 13 T4, 18 N0, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (+/- inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one to two month gap (15-20 Gy). The median follow-up was 29 months.


RESULTS
One patient died of a pulmonary embolism on day 4. All patients received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% after treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomy-free, relapse-free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% and 63%, respectively.


CONCLUSIONS
Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.
Peiffert
D
D
Centre Alexis Vautrin, Nancy, France. d.peiffert@nancy.fnclcc.fr
Giovannini
M
M
Ducreux
M
M
Michel
P
P
François
E
E
Lemanski
C
C
Mirabel
X
X
Cvitkovic
F
F
Luporsi
E
E
Conroy
T
T
Gérard
J P
JP
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D011829:Radiation Dosage; D016879:Salvage Therapy
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil