Application of Chemotherapy

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Application of Chemotherapy
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Solution

• Normal saline Cisplatin , Doxorubicin ,
• Epirubicin , Methotraxate , Vinblastine ,
• Melphalan (phenytoin , heparin ---)
• D5W Oxaliplatin , Carboplatin (amphotericin
  
• B , levophed , --)
• Ringer solution high dose Ara-C

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Class of Chemotherapy

• Alkylating agent mustargen
  cyclophosphamide ifosfomide
  melphalan
• Cisplatin and its analogue carboplatin
  oxaliplatin
• Antimetabolite methotrexate
  5-FU Fludarabine gemcitabine Ara-C
• Topoisomerase inhibitor ectoposide (II)
  irinotecan (I) topotecan (I)
  Adriamycin
• Antimicrotubule vinca alkaloid
  (vincristine , vinblastine , vinorelbine) taxane
  (paclitaxel , docetaxel)

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Complications of Treatment

• Extravasation
• Anaphylaxis
• Myelosuppression
• GI toxicity
• Tumor lysis syndrome
• Interstitial pneumonitis
• Hemorrhagic cystitis

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Class of Skin Toxicity

• Vesicants
• Anthracycline Doxorubicin ,
  Epirubicin Vinca alkaloid Vincristine ,
  Vinblastine Mitomycin-C
• Irritants Etoposide , BCNU , DTIC ,
  Cisplatin Paclitaxel , Mitoxantrone

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Management of Extravasation

• Stop injection
• Extract drug before removing the
• catheter
• Heat pack Vinblastine , Vincristine
• Cold pack others
• Surgery consult surgeon in persistent
• pain (gt72 hours) or local necrosis
• Antidote

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Antidote in Extravasation

• DMSO (dimethyl sulfoxide) local
  packing Mitomycin , Doxorubicin , Epirubicin
• Hyaluronidase local injection Vinblastine ,
  Vincristine , Etoposide
• Sodium thiosulfate Mechlorethamine ,
  Cisplatin

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Nausea and Vomiting(I)

• High emetic potential(gt90)
• (1)Cisplatingt50 mg/m2 (2)Dacarbazine
• (3)Nitrogen mustard (4)Streptozotocin
• (5)MTXgt1500 mg/m2
• Moderately high emeticpotential(6090)
• (1)Carboplatin (2)Cisplatinlt50mg/m2
• (3)Procarbazine (4)Doxorubicin
• (5)Cytarabinegt1g/m2 (6)MTXgt1g/m2

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Antiemetics

• Serotonin receptor antagonists
• Corticosteroids
• Metoclopramide proclorperazine
• Diphenhydramine(Venan)
• Benzodiazepine

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Tumor Lysis Syndrome(I)

• Acute leukemia, high-grade NHL etc.
• Hyperkalemia, hyperuricemia, hyperphosphatemia
• ARF / Seizure / Arrythmias

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Anthracycline

• Doxorubicin , Daunorubicin , Idarubicin ,
  Epirubicin
• CHOP in NHL , I3A7 in AML , VAD in MM
• CAF or CEF or AC in breast cancer
• Toxicity myelosuppression , vomiting ,
  mucositis , cardiomyopathy
• Slowly iv push or drip , except VAD in MM (9mg 24
  hrs for 4 days , for lowering toxicity)

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Anthracycline with CHF

• CHF rare if doxorubicin lt 450 mg/m2
  550 ,600 ,700 mg/m2 ? 7 ,15 ,30
• Recommended dose A 250- 300mg/m2
  (20-25mg/m2/wk)
• E 600-720mg/m2 (30-35mg/m2/wk)
• Toxicity
• Myelosuppression --- A/E 11.2
  Nonhemotologic --- A/E 1 1.5 Cardiotoxicit
  y --- A/E 11.8

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Anthracycline in AML

• 1960 Daunorubicin 30mg ? 50mg
• 1982 Daunorubicin 45mg gt Daunorubicin 30mg
  Doxorubicin 30mg (GI toxicity)
• 1990 3 phase III study
• Idarubicin 12mg gt Daunorubicin 45mg
  ? I3A7 standard treatment ??
• Criticism
• Daunorubicin 70mgIdarubicin 12mg

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Methotrexate (1)

• High dose MTX MTX gt 500mg/m2 , need
• hydration , urine alkalinization and LV
  rescue
• Toxicity Myelosuppression Mucositis
  Renal toxicity and liver toxicity
  Neurotxicity systemic acute
  cerebral dysfunction intrathecal acute
  arachnoiditis subacute arachnoididitis
  chronic encephalopathy
• Only one drug for serum level

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Methotrexate (2)

• Hydration 12 hours before MTX , 24-48 hrs after
  stopping MTX , keep u/o 1500-2000cc/day
• Urine alkalinization keep PHgt7.0 , if initially
  PHgt7.0 ---gt Bicarbona 45-50meq/L
• LV rescue 24 hours after starting MTX
  10-15mg iv q6h 2 days --gt serum level

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Cyclophosphamide (Endoxan)

• Used in lymphoma , breast cancer , ovarian
• cancer , small cell lung cancer ----
• Dose responsive ? BMT or PBSC harvest
• Low dose 100mg/d po for autoimmune dz
• Intermediate dose 600-750 mg/m2 iv d 30min
  
• in NHL or breast cancer
• High dose 4g/m2 ivd 1-2 hrs with Mesna use
  
• for hemorrhagic cystitis risk of
  fulminant cardiac toxicity

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Cytosine Arabinoside (Ara-C)

• Low dose 100mg/m2/d iv infusion 24 hrs
• High dose 2-3 g/m2 ivdrip 1-3 hrs
• I3A7 , I2A5 or I3HDAC , HDAC ---
• Inhibit by Fludarabine (FLAG)
• Toxicity
• neurological toxicity in HDAC
• (cerebellar dysfunction 15 within 8
  
• days , seizure , peripheral
  neuropathy --)
• Ara-C syndrome fever , myalgia , rash ,
  conjunctivitis ? steroid

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L-asparaginase

• CALGB 8811 6000IU/m2 IF 30mins D5,8 ---
• (reduce toxicity after oncovin
  ,prednisolone)
• L-asparagine nonessential amino acid
• lack of synthesis in lymphoid
  malignancy
• Toxicity
• hypersensitivity (lt10) skin test ?
• hypofibrinogenemia , bleeding ,
  thrombosis
• acute pancreatitis

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Cisplatin

• In 0.9 saline 500-1000 cc
• Hydration 3000cc N/S with diuretics
• 80-100 mg/m2 iv 1-3 hrs q3w
• 35 mg/m2 iv 24hrs q1w
• Premedication steroid and serotonin antagonist

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Toxicity of Platinum
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Carboplatin

• Equal efficacy NSCLC , extensive SCLC and
  suboptimally debulking ovarian cancer
• Inferior in head and neck cancer , germ cell
  cancer and esophageal cancer
• Dose (mg) target AUC (4-6) (GFR25) -----
  Calvert formula
• In D5W 250ml iv 2 hours
• Health insurance 1. ovarian cancer 2.
  Ccr lt60 or nephrectomy

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Oxaliplatin

• 130 mg/m2 in D5W iv 2 hrs q3w
• 85 mg/m2 in D5W iv 2 hrs q2w
• 65 mg/m2 in D5W iv 1-2 hrs q1w
• Acute laryngodysesthesia
• Cumulative peripheral neuropathy ---- Ca
  , Mg (?) , glutathione , Tegretol
• Effect ? side effect (CPT-11 side effect ?
  effect)

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Paclitaxel (Taxol) (1)

• Ovary , breast , lung , and 2nd line of Kaposis
  
• sarcoma , NHL
• Dosage 175mg/m2 iv 3 or 24 hrs , q3w
  75 mg /m2 iv 1 or 3 hrs , q1w
• Longer infusion duration , more toxicity and not
  
• necessarily optimal antitumor activity
• Diluted in glass or polypropylene bottle and
  line
• Toxicity Myelosuppression - D8 to D10
  Peripheral neuropathy -- with cisplatin
  
• Cardiac toxicity with
  doxorubicin Extravasation moderate injury
  Hypersensitivity

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Paclitaxel (Taxol) (2)

• Premedication Dexamethasone 20mg po or
  iv , 12 and 6 hours before Taxol
  H1-receptor antagonist Vena 50mg iv 30
  mins before Taxol H2-receptor antagonist
  Zantac 150mg iv 30 mins before Taxol
• Metabolism liver , renal (only 14)
• Drug sequence PC or TG

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Docetaxel (Taxotere) (1)

• Breast , NSCLC , Ovarian caner
• Dosage 75 mg/m2 or 100 mg/m2 iv 1 hour
  q3w
• Diluted in glass or polypropylene bottle and
  line
• Toxicity Hypersensitivity
  minor Fluid retention syndrome (3rd space)
  (usually in cumulative dose gt 400mg/m2) (tx
  stop Taxotere , Aldactone) Neurotoxicity less
  severe

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Docetaxel (Taxotere) (2)

• Premedication Dexamethasone 8mg po D-1
  or D-2 for 3-5 days (-) H1 or H2
  antagonist iv 30 mins before Taxotere
• Metabolism liver

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Chemoprotectant

• Mesna to prevent hemorrhage cystitis
  
• Ifosfamide -15min , 4 , 8 hours ?20 ,
  or continuous infusion
• Cyclophosphamide 60-120 dose
• Dexrazoxane to prevent cardiotoxicity
• Anthracycline in advanced breast cancer
• Amifostine to prevent CDDP neurotoxicity and
  radiation related xerostomia and mucositis

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Irinotecan (CPT-11)

• Topoisomerase 1 inhibitor , use in colon cancer
• 350 mg/m2 iv 30-60 mins q3w
• 100-130 mg/m2 iv 30 mins q1w
• Toxicity myelosuppression
  cholinergic syndrome (flush , tearing ,
  abdominal pain , diarrhea)
• ---- atropine ¼ vial sc or ivdrip
  delayed diarrhea ---- imodium 2
  after each diarrhea then 2 3

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HDFL
- with unique metabolic encephalopathy in 5 of
Taiwanese
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See You Next Time !!