Chemoradiation therapy

The Anal Cancer Trial (ACT I) from the United Kingdom Co-ordinating Committee on Cancer Research demonstrated the superiority of chemoradiation with 5-FU and mitomycin over radiation therapy alone with regard to local failure and deaths from anal cancer.[2,8][Level of evidence A1]In this prospective trial, 585 patients were randomly assigned to receive 45 Gy of radiation in 20 or 25 fractions with or without 5-FU. The 5-FU was given by continuous infusion (750 mg/m2 for 5 days or 1,000 mg/m2 for 4 days) during the first and final weeks of radiation therapy, along with a single dose of mitomycin (12 mg/m2) on the first day.

The Anal Cancer Trial (ACT I) from the United Kingdom Co-ordinating Committee on Cancer Research demonstrated the superiority of chemoradiation with 5-FU and mitomycin over radiation therapy alone with regard to local failure and deaths from anal cancer.[2,8][Level of evidence A1]In this prospective trial, 585 patients were randomly assigned to receive 45 Gy of radiation in 20 or 25 fractions with or without 5-FU. The 5-FU was given by continuous infusion (750 mg/m2 for 5 days or 1,000 mg/m2 for 4 days) during the first and final weeks of radiation therapy, along with a single dose of mitomycin (12 mg/m2) on the first day.

After a median follow-up of 13.1 years, patients who received chemoradiation therapy had a reduction in local failure (36% vs. 59%; hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.35−0.60; P < .001), risk of death from anal cancer (HR, 0.61; 95% CI, 0.49−0.76; P < .001), and relapse at 12 years (17.7% vs. 29.7%; HR, 0.70; 95% CI, 9.58−0.84; P < .001).[2][Level of evidence A1]

The Anal Cancer Trial (ACT I) from the United Kingdom Co-ordinating Committee on Cancer Research demonstrated the superiority of chemoradiation with 5-FU and mitomycin over radiation therapy alone with regard to local failure and deaths from anal cancer.[2,8][Level of evidence A1]In this prospective trial, 585 patients were randomly assigned to receive 45 Gy of radiation in 20 or 25 fractions with or without 5-FU. The 5-FU was given by continuous infusion (750 mg/m2 for 5 days or 1,000 mg/m2 for 4 days) during the first and final weeks of radiation therapy, along with a single dose of mitomycin (12 mg/m2) on the first day.

There was no significant difference in overall survival (OS) in this trial (HR, 0.86; 95% CI, 0.70−1.04; P = .12).

The Anal Cancer Trial (ACT I) from the United Kingdom Co-ordinating Committee on Cancer Research demonstrated the superiority of chemoradiation with 5-FU and mitomycin over radiation therapy alone with regard to local failure and deaths from anal cancer.[2,8][Level of evidence A1]In this prospective trial, 585 patients were randomly assigned to receive 45 Gy of radiation in 20 or 25 fractions with or without 5-FU. The 5-FU was given by continuous infusion (750 mg/m2 for 5 days or 1,000 mg/m2 for 4 days) during the first and final weeks of radiation therapy, along with a single dose of mitomycin (12 mg/m2) on the first day.

An initial 9.1% increase in non–anal cancer deaths was observed in the first 5 years after chemoradiation therapy but was not seen at 10 years.

A European Organisation for Research and Treatment of Cancer (EORTC) trial prospectively randomly assigned 100 patients with T3 to T4 or N1 to N3 disease to receive 45 Gy of radiation with a 15-Gy or 30-Gy boost with or without 5-FU infusion (750 mg/m2 for 5 days starting on days 1 and 29) plus mitomycin (15 mg/m2 on day 1).[3][Level of evidence B1]

A European Organisation for Research and Treatment of Cancer (EORTC) trial prospectively randomly assigned 100 patients with T3 to T4 or N1 to N3 disease to receive 45 Gy of radiation with a 15-Gy or 30-Gy boost with or without 5-FU infusion (750 mg/m2 for 5 days starting on days 1 and 29) plus mitomycin (15 mg/m2 on day 1).[3][Level of evidence B1]

Outcomes favored chemoradiation therapy with respect to 5-year colostomy-free survival rates (75% vs. 48%; P = .002) and 5-year progression-free survival (PFS) rates (60% vs. 48%; P = .05).

A Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group trial of 310 patients studied chemoradiation therapy (5-FU infusion + 45 Gy of radiation) with or without mitomycin.Two large intergroup trials studied the substitution of cisplatin for mitomycin, with differing conclusions.

A Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group trial of 310 patients studied chemoradiation therapy (5-FU infusion + 45 Gy of radiation) with or without mitomycin.Two large intergroup trials studied the substitution of cisplatin for mitomycin, with differing conclusions.

After 4-years of follow-up, patients who received mitomycin had an improved colostomy-free survival rate (71% vs. 59%; P = .014) and disease-free survival (DFS) rate (73% vs. 51%; P = .0003).[9][Level of evidence B1]

In a phase III U.S. Intergroup trial (RTOG 9811 [NCT00003596]), patients in the cisplatin arm received two cycles of induction 5-FU and cisplatin before receiving concurrent chemoradiation therapy with 5-FU and cisplatin.[6]

In a phase III U.S. Intergroup trial (RTOG 9811 [NCT00003596]), patients in the cisplatin arm received two cycles of induction 5-FU and cisplatin before receiving concurrent chemoradiation therapy with 5-FU and cisplatin.[6]

Patients who received mitomycin had improved local control and an improved colostomy-free survival rate (90% vs. 81%; P = .02). Subsequent long-term follow-up demonstrated a borderline significant difference in the 5-year colostomy-free survival rate (71.9% vs. 65%; P = .05).[10]

In a phase III U.S. Intergroup trial (RTOG 9811 [NCT00003596]), patients in the cisplatin arm received two cycles of induction 5-FU and cisplatin before receiving concurrent chemoradiation therapy with 5-FU and cisplatin.[6]

Long-term follow-up also demonstrated a superior 5-year DFS rate (67.8% vs. 57.8%; P = .006) and OS rate (78.3% vs. 70.7%; P = .074) for patients who received mitomycin.[11][Level of evidence B1]

In a phase III U.S. Intergroup trial (RTOG 9811 [NCT00003596]), patients in the cisplatin arm received two cycles of induction 5-FU and cisplatin before receiving concurrent chemoradiation therapy with 5-FU and cisplatin.[6]

One potential explanation for the inferiority of cisplatin in this study was the delay in time to radiation therapy during induction chemotherapy.

In the prospective randomized ACT II trial, 940 patients were assigned in a 2 × 2 factorial design to receive the following: (1) either mitomycin or cisplatin during induction chemoradiation therapy and (2) either maintenance therapy with 5-FU and cisplatin in weeks 11 and 14 or no maintenance therapy.[7]

In the prospective randomized ACT II trial, 940 patients were assigned in a 2 × 2 factorial design to receive the following: (1) either mitomycin or cisplatin during induction chemoradiation therapy and (2) either maintenance therapy with 5-FU and cisplatin in weeks 11 and 14 or no maintenance therapy.[7]

The complete remission rate was equivalent in patients who received mitomycin or cisplatin after a median follow-up of 5.1 years (90.5% vs. 89.6%; 95% CI, -4.9 to 3.1; P = .64). The 3-year PFS rate was also equivalent in both study groups (73% for mitomycin vs. 72% for cisplatin; HR, 0.95; 95% CI, 0.75−1.19; P = .063).[7][Level of evidence B1]

In the prospective randomized ACT II trial, 940 patients were assigned in a 2 × 2 factorial design to receive the following: (1) either mitomycin or cisplatin during induction chemoradiation therapy and (2) either maintenance therapy with 5-FU and cisplatin in weeks 11 and 14 or no maintenance therapy.[7]

There was also no significant effect on 3-year PFS rates among patients who received maintenance therapy or no maintenance therapy (74% vs. 73%; HR, 0.95; 95% CI, 0.75−1.21; P = .70).

In the prospective randomized ACT II trial, 940 patients were assigned in a 2 × 2 factorial design to receive the following: (1) either mitomycin or cisplatin during induction chemoradiation therapy and (2) either maintenance therapy with 5-FU and cisplatin in weeks 11 and 14 or no maintenance therapy.[7]

This study suggests that cisplatin might reasonably substitute for mitomycin in a chemoradiation strategy.