Mitomycin-C– or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

Olivatto, Luis O.; Cabral, Vânia; Rosa, Arthur Accioly; Bezerra, M.; Santarem, E M M; Fassizoli, Ana L.; Castro, Leonaldson; Simões, José Humberto; Small, I. A.; Ferreira, Carlos Gil

doi:10.1016/j.ijrobp.2009.11.057

Cited by 35 publications

(20 citation statements)

References 27 publications

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“…Analysis of toxicity profile of all 23 patients accrued in this study demonstrated that G3/G4 rates of diarrhea and infection seem to be twice as frequent than those rates experienced in other anal cancer trials (21%-31%). 1,14 In general, treatment-related toxicities in this trial were associated with interruption of RT in 15 patients (65%), hospitalization in 12 (52%), and omission of more than 2 cetuximab doses in 5 individuals (17.4%). The contribution of a synergistic effect of cetuximab on these toxicities is possible.…”

Section: Discussionmentioning

confidence: 88%

Phase 1 study of cetuximab in combination with 5‐fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma

Olivatto

Vieira

Pereira

et al. 2013

Cancer

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BACKGROUND: This study sought to determine the feasibility and recommended phase 2 dose (RP2D) of the combination of cetuximab with chemoradiotherapy based on 5-fluorouracil (5-FU) and cisplatin (CP) in locally advanced anal canal carcinoma. METHODS: Cetuximab was administered on days 1,8,15, 29, 36, 43, and 50 (400 mg/m 2 initial dose, then 250 mg/m 2 /week) concurrent with total dose radiation of 55 to 59 Gy, both starting on day 1. Escalating doses of 5-FU (96-hour infusion) and CP (2-hour infusion), both on days 1 and 29, were administered according to the following design: starting dose level (0) 5-FU/CP 5 800/60 mg/m 2 /day and up to dose level (12) 5-FU/CP 5 1000/80 mg/m 2 /day. RESULTS: Dose-limiting toxicity (DLT) events (uncontrolled diarrhea or febrile neutropenia) occurred in 3 of 14 assessable patients receiving escalated dose of 5-FU/CP, with 1 in dose level (0) and 2 in dose level (12). The RP2D was 5-FU/CP 5 800/80 mg/m 2 /day. Because of unexpected non-DLT treatment-related grade 3 (G3) adverse events (AEs) such as thrombosis/embolism, syncope, and infection occurring in 20% of patients, a safety expansion cohort with an additional 9 patients was investigated with the RP2D. The most frequent G3/G4 AEs evaluated in 23 patients were radiation dermatitis (12 patients), diarrhea (10 patients), thrombosis/embolism (6 patients), and infection (5 patients). The study was closed due to these severe AEs, although no G5 AEs occurred. Twenty of 21 patients (95%) achieved pathological complete response at primary tumor. With a median follow-up of 43.4 months, the 3-year locoregional control rate was 64.2%. CONCLUSIONS: Cetuximab could not be integrated with chemoradiotherapy-cisplatin-based therapy due to the high toxicity rate. However, efficacy is encouraging and further investigation of an epidermal growth factor receptor-targeted agent (other than cetuximab) concurrent with chemoradiation should be pursued. Cancer 2013;119:2973-80.

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Section: Discussionmentioning

confidence: 88%

Phase 1 study of cetuximab in combination with 5‐fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma

Olivatto

Vieira

Pereira

et al. 2013

Cancer

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“…In large retrospective studies, good results have been shown with cisplatin-based regimens compared with standard mmc treatment 16,17 . However, two phase iii trials failed to demonstrate superiority for cisplatin compared with mmc for the treatment of acc.…”

Section: Discussionmentioning

confidence: 99%

One Compared with Two Cycles of Mitomycin C in Chemoradiotherapy for Anal Cancer: Analysis of Outcomes and Toxicity

et al. 2014

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(1) Background: Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation. However, administration of the second bolus of mmc has been based largely on centre preference. Given limited published data on outcomes with different mmc regimens, our objective was to compare the efficacy and toxicity of 1 compared with 2 cycles of mmc in acc treatment. (2) Methods: Our retrospective study evaluated 169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free (dfs) and overall survival (os) were analyzed. (3) Results: Baseline demographics, performance status, and stage were similar in the groups of patients who received mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were comparable, except for white blood cell count, which was higher in the mmc2 group, but within normal range. The 5-year os and dfs were similar (75.1% and 54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively). On multivariate analysis, mmc2 was the factor most strongly associated with specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01), grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001). (4) Conclusions: In definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes similar to those achieved with 2 cycles, with significantly less acute toxicity.

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“…Recently, a similar study with long term follow up, including 57% patients with T3-T4 disease has confirmed the good results of chemo-radiotherapy combining CP plus 5-fluorouracil. This regimen seems to provide comparable results to those achieved with MMC plus 5-fluorouracil [37]. In patients with for locally advanced canal anal carcinoma, a multicenter French phase III study (ACCORD 03) randomized a concomitant radio-chemotherapy with cisplatin plus 5-fluorouracil versus the same CRT following two cycles of neoadjuvant chemotherapy (cisplatin plus 5-fluorouracil).…”

Section: Discussionmentioning

confidence: 99%

Is neoadjuvant chemotherapy prior to radio‐chemotherapy beneficial in T4 anal carcinoma?

Moureau-Zabotto

Viret

Giovaninni

et al. 2011

Journal of Surgical Oncology

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Mitomycin-C– or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

Cited by 35 publications

References 27 publications

Phase 1 study of cetuximab in combination with 5‐fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma

Phase 1 study of cetuximab in combination with 5‐fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma

One Compared with Two Cycles of Mitomycin C in Chemoradiotherapy for Anal Cancer: Analysis of Outcomes and Toxicity

Is neoadjuvant chemotherapy prior to radio‐chemotherapy beneficial in T4 anal carcinoma?

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