Basics of Chemotherapy


Short-term infusional fluorouracil and leucovorin for gastrointestinal cancer (modified de Gramont schedule) [2]

Each cycle is 14 days

Drug

Dose/route

Administration

 Leucovorin

400 mg/m2 IV

Day 1 given over 2 h

 5-FU bolus

400 mg/m2 IV

Day 1 given after leucovorin

 5-FU infusional

2400 mg/m2 IV

Given over 46 h via pump

Weekly bolus fluorouracil plus high-dose leucovorin (Roswell Park Memorial Institute regimen) [3]

Treatment consists of four cycles (8 weeks per cycle)

 Leucovorin

500 mg/m2 IV

Weekly for 6 weeks (days 1, 8, 15, 22, 29, 36)

 5-FU bolus

500 mg/m2 IV

Weekly for 6 weeks (days 1, 8, 15, 22, 29, 36)

Adjuvant capecitabine [4]

 Capecitabine

1250 mg/m2 oral

Twice daily on day 1 through 14 every 21 days





 

  • (iii)


    Toxicity: myelotoxicity, diarrhea, mucositis, renal toxicity, palmar-plantar erythrodysesthesia (hand-foot syndrome), angina (coronary vasospasm), fatigue, anorexia, and nausea/vomiting:


    1. (1)


      Dihydropyrimidine dehydrogenase (DPD) deficiency: Patients who are partially or totally deficient in DPD cannot adequately degrade fluoropyrimidine therapies, resulting in an increased risk of severe, and even fatal, toxicity. Fluorouracil (FU)-based therapy should be avoided in patients with DPD deficiency, and tests are available to test for the deficiency.

       

     






       

    1. (b)


       Oxaliplatin-containing chemotherapy:


      1. (i)


        Mechanism of action: Oxaliplatin is a platinum-derivative, alkylating agent. The platinum compound binds to DNA forming cross-links and inhibits DNA replication and transcription, which results in cell death.

         

      2. (ii)


        Schedule (Table 1.2).


        Table 1.2
        Oxaliplatin-containing regimens treatment schedule








































        Modified FOLFOX6 chemotherapy [2]

        Each cycle is 14 days

        Drug
        Dose/route
        Administration

        Oxaliplatin
        85 mg/m2 IV
        Day 1 can give concurrently with leucovorin

        Leucovorin
        400 mg/m2 IV
        Day 1 given over 2 h

        5-FU bolus
        400 mg/m2 IV
        Day 1 given after leucovorin

        5-FU infusional
        2400 mg/m2 IV
        Given over 46 h via pump

        Capecitabine and oxaliplatin (CAPOX) [2]

        Each cycle is 21 days

        Oxaliplatin
        130 mg/m2 IV
        Day 1 given over 2 h

        Capecitabine
        850 mg/m2 oral
        Twice daily from day 1 (pm) to day 15 (am)

         

      3. (iii)


        Toxicity: myelotoxicity, peripheral neuropathy (paresthesias and dysesthesias), nausea/vomiting, diarrhea, fatigue, anorexia, hepatotoxicity, and alopecia.

         

       

    2. (c)


       Adjuvant radiation therapy (RT):


      1. (i)


        Not usually considered a routine component of care for completely resected colon cancer

         

      2. (ii)


        May be considered for patients with ascending or descending colon primary with T4 disease or for patients who have a positive resection margin

         

       






         

      1. 3.


        Metastatic colon cancer: Eight classes of drugs have been shown to have activity in metastatic colon cancer: (1) 5-FU-based therapies, (2) oxaliplatin-containing, (3) irinotecan-containing, (4) epidermal growth factor receptor (EGFR)-targeting therapies (cetuximab and panitumumab), (5) bevacizumab, (6) intravenous aflibercept, (7) regorafenib, and (8) trifluridine-tipiracil (TAS-102):


        1. (a)


          EGFR-targeting therapies (cetuximab and panitumumab): appropriate only for patients with KRAS/NRAS wild-type tumors


          1. (i)


            Mechanism of action: monoclonal antibodies (MoAbs) directed against the epidermal growth factor receptor (EGFR). Inhibits cell growth by blocking phosphorylation and activation of receptor-associated kinases

             

          2. (ii)


            Schedule (Table 1.3)


            Table 1.3
            EGFR-targeting therapies’ treatment schedule





























            Cetuximab [6]

            Each cycle is 1 week

            Drug
            Dose/route
            Administration

            Cetuximab
            400 mg/m2 IV
            Day 1

            Cetuximab
            250 mg/m2 IV
            Weekly, starting with cycle 2

            Panitumumab [7]

            Each cycle is 2 weeks
            		    

            Panitumumab
            6 mg/kg IV
            Day 1

             

          3. (iii)


            Toxicity: dermatologic (acneiform rash), stomatitis, keratitis (panitumumab), pulmonary fibrosis/interstitial lung disease (panitumumab), fatigue, neuropathy, diarrhea, and nausea

             

           

        2. (b)


           Bevacizumab


          1. (i)


            Mechanism of action: a monoclonal antibody targeting vascular endothelial growth factor (VEGF)

             

          2. (ii)


            Schedule (Table 1.4)


            Table 1.4
            Bevacizumab treatment schedule






















            Bevacizumab

            Drug
            Dose/route
            Administration

            Bevacizumab (combined with capecitabine) [8]
            7.5 mg/kg IV
            Day 1 of 21 day cycles

            Bevacizumab (combined with FOLFOX or FOLFIRI) [2, 9]
            5 mg/kg IV
            Day 1 of 14 day cycles

             

          3. (iii)


            Toxicity: hypertension, venous and arterial thromboembolism, hemorrhage, gastrointestinal perforation, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome, peripheral edema, and fatigue

             

           

        3. (c)


           Intravenous aflibercept


          1. (i)


            Mechanism of action: a recombinant fusion protein comprised of portions of binding domains for VEGF receptors 1 and 2 acts as a decoy receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF) which works to prevent angiogenesis.

             

          2. (ii)


            Schedule (Table 1.5).


            Table 1.5
            Intravenous aflibercept treatment schedule


















            Intravenous aflibercept

            Drug
            Dose/route
            Administration

            Intravenous aflibercept (combined with FOLFIRI) [10]
            4 mg/kg IV
            Day 1 of 14 day cycles

             

          3. (iii)


            Toxicity: hypertension, bleeding, proteinuria, wound infection, thromboembolic events, diarrhea, mucositis, neutropenia, and fatigue.

             

           

        4. (d)


           Regorafenib


          1. (i)


            Mechanism of action: orally active angiogenic tyrosine kinase inhibitor (including the VEGF receptors 1 to 3), as well as other receptor and intracellular kinases

             

          2. (ii)


            Schedule (Table 1.6)


            Table 1.6
            Regorafenib treatment schedule


















            Regorafenib

            Drug
            Dose/route
            Administration

            Regorafenib [11]
            160 mg oral
            Daily for three of every 4 weeks

             

          3. (iii)


            Toxicity: hypertension, fatigue, diarrhea, rash, hematologic, infection, and proteinuria

             

           

        5. (e)


           Trifluridine-tipiracil (TAS-102)


          1. (i)


            Mechanism of action: an oral cytotoxic agent consisting of the nucleoside analog trifluridine (a cytotoxic antimetabolite that inhibits thymidylate synthetase) and tipiracil, a thymidine phosphorylase inhibitor, which inhibits trifluridine metabolism and also has antiangiogenic properties

             

          2. (ii)


            Schedule (Table 1.7)


            Table 1.7
            TAS-102 treatment schedule


















            TAS-102

            Drug
            Dose/route
            Administration

            TAS-102 [12]
            35 mg/m2 oral
            Twice daily on days 1–5 and 8–12 of 28-day cycles

             

          3. (iii)


            Toxicity: fatigue, nausea, anorexia, diarrhea, and hematologic

             

          4. (f)


             Irinotecan-containing chemotherapy:


            1. (i)


              Mechanism of action: Irinotecan is converted to SN-38 (active metabolite) and binds reversibly to the topoisomerase I-DNA complex which ultimately leads to double-strand DNA breaks and termination of cellular replication.

               

            2. (ii)


              Schedule (Table 1.8).


              Table 1.8
              Irinotecan-containing regimens treatment schedule






























              FOLFIRI chemotherapy [5]

              Each cycle is 14 days

              Drug
              Dose/route
              Administration

              Irinotecan
              180 mg/m2 IV
              Day 1 can give concurrently with leucovorin

              Leucovorin
              400 mg/m2 IV
              Day 1 given over 2 h

              5-FU bolus
              400 mg/m2 IV
              Day 1 given after leucovorin

              5-FU infusional
              2400 mg/m2 IV
              Given over 46 h via pump

               

            3. (iii)


              Toxicity: myelotoxicity, diarrhea, nausea/vomiting, dehydration, fatigue, anorexia, hepatotoxicity, and alopecia.

               

             

           

         






          1.2 Rectal Cancer





          1. 1.


            Neoadjuvant therapy


            1. (a)


              Infusional 5-FU during neoadjuvant chemoradiotherapy (225 mg/m2/d Monday–Friday every week or 7 days/week).

               

            2. (b)


              Capecitabine concurrent with neoadjuvant chemoradiotherapy (825 mg/m2/ po bid Monday–Friday every week or 7 days/week).

               

            3. (c)


              Oxaliplatin or irinotecan in addition to 5-FU-based chemotherapy is not considered a standard approach.

               

             

          2. 2.


            Adjuvant therapy


            1. (a)


              Adjuvant fluoropyrimidine-based chemotherapy is recommended for most patients:


              1. (i)


                Options include LV-modulated 5-FU, fluoropyrimidine monotherapy, FOLFOX, or capecitabine plus oxaliplatin (XELOX).

                 

               

             

          3. 3.


            Metastatic


            1. (a)


              Potentially resectable metastases: Options include neoadjuvant chemotherapy followed by resection (synchronous or staged) and postoperative fluoropyrimidine-based chemoradiotherapy, neoadjuvant chemotherapy followed by chemoradiotherapy and then resection, or initial surgery followed by chemotherapy alone for pT1-2 N0 disease or chemotherapy plus RT for more advanced T-stage or node-positive disease.

               

            2. (b)


              Unresectable metastatic disease: Treatment depends on the symptomatic nature of the disease.


              1. (i)


                Symptomatic: systemic chemotherapy, chemoradiotherapy, surgery of involved rectal segment, or stenting

                 

              2. (ii)


                Asymptomatic: follows similar guidelines as outlined above for metastatic colon cancer

                 

               

             


          1.3 Anal Cancer





          1. 1.


            Neoadjuvant therapy


            1. (a)


              Concurrent use of fluorouracil (FU) plus mitomycin during radiation therapy


              1. (i)


                Mitomycin mechanism of action: inhibits DNA and RNA synthesis and produces DNA cross-linking similar to an alkylating agent

                 

              2. (ii)


                Schedule (Table 1.9)


                Table 1.9
                Concurrent 5-FU plus mitomycin during RT treatment schedule






















                5-FU plus mitomycin with concurrent RT [13]

                Drug
                Dose/route
                Administration

                Mitomycin
                10 mg/m2 IV
                Days 1 and 29

                5-FU
                1000 mg/m2 per day IV
                Continuous infusion on days 1–4 and days 29–32

                 

              3. (iii)


                Toxicity: myelotoxicity, local skin reaction, diarrhea, stomatitis, thrombotic microangiopathy, pulmonary toxicity, fever, alopecia, nausea, and vomiting

                 

               

            2. (b)


               Concurrent use of fluorouracil (FU) plus cisplatin during radiation therapy


              1. (i)


                Cisplatin mechanism of action: inhibits synthesis of DNA by forming DNA cross-links

                 

              2. (ii)


                Schedule (Table 1.10)


                Table 1.10
                Concurrent 5-FU plus cisplatin during RT treatment schedule






















                5-FU plus cisplatin with concurrent RT [14]

                Drug
                Dose/route
                Administration

                Cisplatin
                75 mg/m2 IV
                Days 1 and 29

                5-FU
                1000 mg/m2 per day IV
                Continuous infusion on days 1–4 and days 29–32

                 

              3. (iii)


                Toxicity: myelotoxicity, diarrhea, stomatitis, nephrotoxicity, neuropathy, ototoxicity, alopecia, nausea, and vomiting

                 

               

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          Oct 18, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Basics of Chemotherapy

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