Table 2.
Studies evaluating recent treatment options in locally advanced anal cancer
| Study | Patients, n | Protocol | RR | OS | DFS | CFS | |
| Induction chemotherapy in LAAC | Nilsson et al[36], 2005Population-based series | 308 invasive SCAC | - Arm A: Neoadjuvant platinum CT followed by RT alone | CR: 92% | 63% | NA | NA |
| 142 locally advanced | -Arm B: RT with or without Bleomycin | CR: 76% P < 0.01 | 44% P < 0.05 | ||||
| Meropol et al[37], 20081 Phase II | 45 | Induction: 2 28-d cycles (FU + cisplatin) followed by 2 28-d cycles (FU + mitomycin) with concurrent split-course radiation | CR: 82% | 68% at 4 yr | 61% at 4 yr | 50% | |
| Peiffert et al[38], 20122 Phase III RCT | 283 | -Arm A: 2 ICT cycles (5-FU + cisplatin) then RCT and standard dose boost (SD: 15 Gy) | NA | NA | NA | 69.6% | |
| -Arm B: 2 ICT, RCT and high dose boost (HD: 20-25 Gy) | 82.4% | ||||||
| -Arm C: RCT and SD boost | 77.1% | ||||||
| -Arm D: RCT and HD boost | 72.7% | ||||||
| Combination of MMC and cisplatin in LAAC | Crehange et al[39], 2007 Phase II | 21 | 1st sequence:RT 36 Gy over 4 wk | CR: 90.5% | NA | NA | NA |
| 2nd sequence: 23.4 Gy over 2.5 wk, gap 16 d | |||||||
| MMC and CDDP | |||||||
| Matzinger et al[40], 20093 Phase II | 80 | RT: 36Gy + 2 wk gap + 23.4 Gy | |||||
| -Arm A: MMC + Cisplatin + RT | RR: 91.9% | NA | NA | NA | |||
| -Arm B: MMC + 5-FU + RT | RR: 79.5% | ||||||
| Targeted therapy in LAAC | Olivatto et al[48], 2013 Phase I | 21 | Cetuximab + RT + 5-FU + cisplatin | pCR: 95% | NA | NA | NA |
| Deutsch et al[49], 2013 Phase II | 16 | Cetuximab + RT + 5-FU + cisplatin | CR: 55%PR: 45% | 92% at 1 yr | NA | 67% at 1 yr | |
| Cisplatin in LAAC | Eng et al[50], 20134 Retrospective single institution analysis | 197 (41% stage II, 46% stage III, 24% N2-N3) | Weekly (20 mg/m2) or daily (4 mg/m2) cisplatin with 5-FU and RT | CR: 94% | 86% at 5 yr | 81% at 5 yr | 88% at 5 yr |
After induction, 8 CR and 21 PR. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation;
Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% vs 75% in groups A and B vs C and D, respectively (ICT effect; P = 0.37), and 73.7% vs 77.8% in groups A and C vs B and D, respectively (RT-dose effect; P = 0.067);
In the first arm, 9 patients discontinued treatment, with 9 grade 3 hematologic effects. In the second arm, 2 discontinued treatment, and no grade 3 hematologic effects were reported;
The local recurrence rate was 11% after the median follow-up of 8.6 yr, and 8% of the patients developed distal metastases. LAAC: Locally advanced anal cancer; MMC: Mitomycin C; RR: Response rate; NA: Not availiable; RT: Radiation therapy; 5-FU: 5-Fluorouracil; CR: Complete response; CFS: Colostomy-free survival; OS: Overall survival; DFS: Disease free survival; RT: Radiation therapy.