Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease
Background: Cancer treatments induce symptoms/signs superimposing on individual patient's clinical status, determining heterogenous toxicity syndromes (TS). We reviewed intensive first line triplet chemotherapy-based regimens in metastatic gastro-intestinal cancers (mGI), based on FIr/FOx sched...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00172/full |
| _version_ | 1818969004588400640 |
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| author | Gemma Bruera Gemma Bruera Enrico Ricevuto Enrico Ricevuto |
| author_facet | Gemma Bruera Gemma Bruera Enrico Ricevuto Enrico Ricevuto |
| author_sort | Gemma Bruera |
| collection | DOAJ |
| description | Background: Cancer treatments induce symptoms/signs superimposing on individual patient's clinical status, determining heterogenous toxicity syndromes (TS). We reviewed intensive first line triplet chemotherapy-based regimens in metastatic gastro-intestinal cancers (mGI), based on FIr/FOx schedule, fluorouracil and weekly alternating irinotecan/oxaliplatin, to point out limiting TS (LTS) relevance.Methods: Metastatic colo-rectal (mCRC), pancreatic ductal adenocarcinoma (mPDAC), gastric carcinoma (mGC) patients were enrolled by careful decision-making including age, performance status (PS), and comorbidity status in real life phase II studies: FIr-B/FOx adding bevacizumab (B) overall, FIr-C/FOx-C adding cetuximab (C) in KRAS/NRAS wild-type mCRC; FIr/FOx in mPDAC; FD/FOx adding docetaxel (D) in mGC. Toxicity, individual LTS, LT alone (LTS-single site, LTS-ss) or associated to other limiting/G2 toxicities (LTS-multiple sites, LTS-ms) were evaluated, compared by chi-square test. In FIr-C/FOx-C, 5-fluorouracil/irinotecan pharmacogenomic biomarkers, 5-fluorouracil degradation rate (5-FUDR), SNPs ABCB1, CYP3A4, DYPD, UGT1A1 were evaluated, related with LTS.Results: FIr-B/FOx, FIr-C/FOx-C in mCRC, FIr/FOx in mPDAC, FD/FOx in mGC, showed activity, efficacy, toxicities similar to reported triplet regimens. LTS: mCRC FIr-B/FOx 44%, LTS-ms 24%, LTS-ss 20%, in young-elderly 46%, LTS-ms significantly increased vs. LTS-ss; FIr-C/FOx-C 65.5%, significantly increased LTS-ms vs. LTS-ss, in young-elderly 83%; mPDAC FIr/FOx 27.5%, mostly LTS-ms, in young-elderly 38.4% all LTS-ms; mGC FD/FOx 30%, all LTS-ms, in young-elderly 25%. Reduced FUDR, SNPs CYP3A4, UGT1A1, >1 positive pharmacogenomic biomarkers were prevalent in patients with gastrointestinal LTS.Conclusions: LTS is an innovative clinical parameter of toxicity burden, differential treatment-related TS in individual patient. LTS can evaluate pharmacogenomic biomarkers predictive relevance to select mGI patients fit for intensive treatments, at risk of limiting gastrointestinal toxicity.Trial Registrations: The trials were registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34, and Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2009- 016793-32. |
| first_indexed | 2024-12-20T14:13:41Z |
| format | Article |
| id | doaj.art-ca203c0743634c94af4d402efbc8f00e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T14:13:41Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-ca203c0743634c94af4d402efbc8f00e2022-12-21T19:38:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00172496141Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic DiseaseGemma Bruera0Gemma Bruera1Enrico Ricevuto2Enrico Ricevuto3Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, ItalyOncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, ItalyBackground: Cancer treatments induce symptoms/signs superimposing on individual patient's clinical status, determining heterogenous toxicity syndromes (TS). We reviewed intensive first line triplet chemotherapy-based regimens in metastatic gastro-intestinal cancers (mGI), based on FIr/FOx schedule, fluorouracil and weekly alternating irinotecan/oxaliplatin, to point out limiting TS (LTS) relevance.Methods: Metastatic colo-rectal (mCRC), pancreatic ductal adenocarcinoma (mPDAC), gastric carcinoma (mGC) patients were enrolled by careful decision-making including age, performance status (PS), and comorbidity status in real life phase II studies: FIr-B/FOx adding bevacizumab (B) overall, FIr-C/FOx-C adding cetuximab (C) in KRAS/NRAS wild-type mCRC; FIr/FOx in mPDAC; FD/FOx adding docetaxel (D) in mGC. Toxicity, individual LTS, LT alone (LTS-single site, LTS-ss) or associated to other limiting/G2 toxicities (LTS-multiple sites, LTS-ms) were evaluated, compared by chi-square test. In FIr-C/FOx-C, 5-fluorouracil/irinotecan pharmacogenomic biomarkers, 5-fluorouracil degradation rate (5-FUDR), SNPs ABCB1, CYP3A4, DYPD, UGT1A1 were evaluated, related with LTS.Results: FIr-B/FOx, FIr-C/FOx-C in mCRC, FIr/FOx in mPDAC, FD/FOx in mGC, showed activity, efficacy, toxicities similar to reported triplet regimens. LTS: mCRC FIr-B/FOx 44%, LTS-ms 24%, LTS-ss 20%, in young-elderly 46%, LTS-ms significantly increased vs. LTS-ss; FIr-C/FOx-C 65.5%, significantly increased LTS-ms vs. LTS-ss, in young-elderly 83%; mPDAC FIr/FOx 27.5%, mostly LTS-ms, in young-elderly 38.4% all LTS-ms; mGC FD/FOx 30%, all LTS-ms, in young-elderly 25%. Reduced FUDR, SNPs CYP3A4, UGT1A1, >1 positive pharmacogenomic biomarkers were prevalent in patients with gastrointestinal LTS.Conclusions: LTS is an innovative clinical parameter of toxicity burden, differential treatment-related TS in individual patient. LTS can evaluate pharmacogenomic biomarkers predictive relevance to select mGI patients fit for intensive treatments, at risk of limiting gastrointestinal toxicity.Trial Registrations: The trials were registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34, and Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2009- 016793-32.https://www.frontiersin.org/article/10.3389/fonc.2020.00172/fullindividual limiting toxicity syndromesintensive first linemetastatic gastrointestinal cancerreal lifetimed-flat-infusion 5-fluorouracil administrationtriplet chemotherapy-based regimens |
| spellingShingle | Gemma Bruera Gemma Bruera Enrico Ricevuto Enrico Ricevuto Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease Frontiers in Oncology individual limiting toxicity syndromes intensive first line metastatic gastrointestinal cancer real life timed-flat-infusion 5-fluorouracil administration triplet chemotherapy-based regimens |
| title | Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease |
| title_full | Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease |
| title_fullStr | Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease |
| title_full_unstemmed | Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease |
| title_short | Toxicity Syndromes, Patient-Related Clinical Indicator of Toxicity Burden Induced by Intensive Triplet Chemotherapy-Based Regimens in Gastrointestinal Cancers With Metastatic Disease |
| title_sort | toxicity syndromes patient related clinical indicator of toxicity burden induced by intensive triplet chemotherapy based regimens in gastrointestinal cancers with metastatic disease |
| topic | individual limiting toxicity syndromes intensive first line metastatic gastrointestinal cancer real life timed-flat-infusion 5-fluorouracil administration triplet chemotherapy-based regimens |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00172/full |
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