Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer

Petrelli, Fausto; Ghidini, Antonio; Inno, Alessandro; Barni, Sandro

doi:10.1097/cad.0000000000000363

Cited by 3 publications

(5 citation statements)

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“…In view of the efficacy and the acceptable-mainly hematologic-toxicity, this combination has been suggested as an alternative therapeutic option for this indication. 15 Fluoropyrimidines in association with mitomycin act synergistically in vitro. 16,17 5-Fluorouracil mitomycin regimen, in association with radiotherapy, constitutes the gold standard for locally advanced forms.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have assessed the association of 5‐FU and mitomycin‐C in patients presenting heavily pretreated metastatic colorectal cancer. In view of the efficacy and the acceptable—mainly hematologic—toxicity, this combination has been suggested as an alternative therapeutic option for this indication . Fluoropyrimidines in association with mitomycin act synergistically in vitro .…”

Section: Introductionmentioning

confidence: 99%

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Mitomycin and 5‐fluorouracil for second‐line treatment of metastatic squamous cell carcinomas of the anal canal

et al. 2019

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BackgroundMetastatic squamous cell carcinomas (SCC) of the anal canal are rare and there is no international consensus on their second‐line management. 5‐Fluorouracil (5‐FU) and mitomycin in combination with radiotherapy is the standard for locally advanced forms but its efficacy in metastatic stage has never been evaluated.Patients and methodsWe report a retrospective analysis of patients treated with 5‐FU and mitomycin from 2000 to 2017 in our institution for a metastatic SCC of the anal canal after failure of platinum‐based regimen. The main outcome was progression‐free survival (PFS) and the secondary outcomes were overall survival (OS), response rate, and toxicity.ResultsNineteen patients, 15 women and four men, with a median age of 57 years were identified (range, 40‐79 years). Patients received a median of three cycles (1‐7) of mitomycin 5‐FU. A dose reduction was necessary in six patients (31.6%), one patient had to discontinue treatment following toxicity and no death was due to treatment toxicity was reported. An objective response was observed in five patients (26.4%, 95% CI 6.6‐46.2) including one complete response, six patients (31.6%, 95% CI 10.7‐52.5) showed tumor stabilization. Median PFS and OS were 3 months [95% CI 1‐5] and 7 months [95% CI 2.2‐11.8]. Responder had a median duration of response of 4 months [95% CI 1.8‐6.1] and one patient had 23 months duration of response. No significant difference was noted for PFS and OS for patients previously treated with mitomycin and 5‐FU at a local stage.ConclusionMitomycin and 5‐FU regimen provides tumor control with acceptable tolerance. It is an option for patients with metastatic SCC of the anal canal after failure of platinum‐based chemotherapy. [Correction added on 9 October 2019, after first online publication: '5‐FU' was inadvertently removed from the Results and Conclusion and has now been added to the text.]

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitomycin and 5‐fluorouracil for second‐line treatment of metastatic squamous cell carcinomas of the anal canal

et al. 2019

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“…With regards to objective response rates (ORRs), 14 patients (17.5%) had PR and 28 (35%) SD, accounting for a 52.5% DCR. These data compare favorably with those achieved with licensed third-line therapies such as the multikinase inhibitor regorafenib (ORR = 1–4%) and the trifluridine–tipiracil combination TAS-102 (ORR = 2%), both of which are administered without the selection of a molecular target, or salvage chemotherapy with mitomycin-C or oxaliplatin rechallenge [17, 22, 23]. …”

Section: Discussionmentioning

confidence: 68%

“…These patients, who had experienced a median number of five lines of previous treatments, achieved a median PFS of 2.8 months (with approximately one-quarter of patients displaying a PFS >5 months) and a median OS of 7.8 months. These data should be evaluated in the context of advanced mCRC, where the median PFS with newer agents has been less than 2 months [20], and rechallenge with standard chemotherapy [18, 19] or further chemotherapy [17] showed only poor efficacy and was burdened by adverse effects [21]. With regards to objective response rates (ORRs), 14 patients (17.5%) had PR and 28 (35%) SD, accounting for a 52.5% DCR.…”

Section: Discussionmentioning

confidence: 99%

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

et al. 2017

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BackgroundPatients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.ObjectiveWe retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).Patients and MethodsFrom June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).ResultsOne patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06).ConclusionsThis single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.

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“…[16][17][18] MMC plus 5-FU are also used for salvage treatment for metastatic colorectal cancer after previous oxaliplatin or target therapy, with favorable toxicity profiles and cost efficacy. [19][20][21] In this study, the toxicity of MMC, including grade 1 and grade 2 neutropenia and thrombocytopenia, was higher when compared with UFUR alone, but there were no significant differences in grade 3 or grade 4 neutropenia or thrombocytopenia, nor were there differences in other toxicity symptoms such as nausea/vomiting between two groups. Overall, the cases of severe toxicity (more than grade 3) were few in our study.…”

Section: Discussionmentioning

confidence: 91%

The effect of Mitomycin-C in neoadjuvant concurrent chemoradiotherapy for rectal cancer

Wang

Liu

Jiang

2022

Journal of the Chinese Medical Association

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Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer

Cited by 3 publications

References 31 publications

Mitomycin and 5‐fluorouracil for second‐line treatment of metastatic squamous cell carcinomas of the anal canal

Mitomycin and 5‐fluorouracil for second‐line treatment of metastatic squamous cell carcinomas of the anal canal

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

The effect of Mitomycin-C in neoadjuvant concurrent chemoradiotherapy for rectal cancer

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