howitreat.in
A user-friendly, frequently updated reference guide that aligns with international guidelines and protocols.
Antineoplastic Agents
Introduction:
- Genetic pleomorphisms (pharmacogenomics) affect drug metabolism and hence degree of toxicity. Hence dose adjustments are needed during therapy.
- In most of the institutes for obese patients, BSA is calculated after taking into account “ideal body weight” as weight of the patient. Also sometimes, BSA is capped at 2m2. But several studies have shown that, there is no increased risk of short term or long term toxicity, in obese patients who have received full weight based doses. In fact, lowering the doses leads to higher chances of treatment failure.
- Side effects:
- Pancytopenia due to bone marrow suppression with nadir on 7th day (Give GCSF/transfusions as required)
- Vomiting (Give Ondansetron)
- Gastritis (Give antacids)
- Mucositis (Give Chlorhexidine mouth wash)
- Thrombophlebitis/ extravasation injury (Administer chemo through central line)
- Alopecia (Reassure)
- Possible infertility (sperm preservation if necessary)
- Highly teratogenic (UPT prior to starting any chemo and avoid pregnancy during therapy)
- Secreted in breast bilk (So breast feeding should be avoided)
- Tumour lysis during 1st chemo
- Chemotherapy should be given as close as possible to their maximum individual doses and should be given as frequently as possible to avoid tumorregrowth. G-CSF may be given to hasten the recovery, so that chemotherapy can be given on time.
- Each cycle kills nearly 99% of cells. Repeat cycles are necessary to eradicate alltumor cells.
- Combination chemotherapy is given, as it takes care of cells that develop resistance against one agent.
- Most of the drugs act on cells which are in S phase of mitosis. Hence tumors with high proliferative activity are highly sensitive to chemotherapy.
- Normal tissues which proliferate faster are also affected (Ex: Bone marrow, hair follicle, intestinal epithelium etc)
- Following factors must be taken intoconsideration while choosing drug regimens for patients
- Renal and hepatic function
- Bone marrow reserve
- General performance status
- Concurrent medical problems
- All chemo to be given in glass bottles/ Baxter pouches
- Avoid chemotherapy if there is active infection
- Avoid chemotherapy if there is history of serious hypersensitivity
Alkylating Agents:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Cyclophosphamide | Depends on protocol | --- | Hepatic correction, renal correction, W/F- Hemorrhagic cystitis (Acrolein), SIADH, For doses >1gm/m2- Hydration- NS 100ml/m2 for 24 hrs with Mesna- 1-1.5 x dose divided into 3 doses (0, 4 and 8 hrs). Give early in the day. Advice to drink plenty of fluids and empty bladder frequently |
| Ifosfamide | Depends on protocol | W/F Neurotoxicity (Altered mental status leading to coma), can cause renal tubular damage, Can casue hemorrhagic cystitis, hence hydration with 60% of total dose mesna has to be given in 3 divided doses (0, 4, 8hrs) | |
| Chlorambucil | 0.1-0.2mg/kg/day | --- | Adjust doses to maintain ANC/PL in acceptable limits |
| Melphalan | Depends on protocol | Monitor CBC,Use with caution in renal impairment, cytopenia | |
| Busulfan | Depends on protocol | For very high doses (BMT) use prophylactic anticonvulsants, In high doses can cause veno occlusive disease | |
| Dacrabazine | Depends on protocol | --- | Renal correction, monitor CBC, LFT, W/F flu like symptoms |
| Bendamustine | Depends on protocol | --- | Renal, hepatic and hematological correction |
Antimetabolites:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Methotrexate | Depends on protocol | --- | Renal correction, hepatic correction, If there is pleural effusion or ascites, drug gets stored in fluid. Later it is released in circulation causing prolonged toxicity. Stop folic acid/ septran/ allopurinol/ pentids/ phenytoin before high dose MTX, For HD MTX- hydration, I/O monitoring, folinic acid rescue, Urine pH monitoring |
| 6-Mercaptopurine | Depends on protocol | --- | Take in evening on empty stomach, avoid milk products after lunch, monitor CBC, LFT, Uric acid, W/F drug induced fever and rash, If TPMT mutation decrease the dose |
| Azathioprine | 1-2mg/kg-OD | >12years- 1-2mg/kg- OD | Monitor CBC, LFT |
| Fludarabine | Depends on protocol | Renal correction, Irradiated blood products, PCP, HSV prophylaxis, W/F- AIHA, cytopenia, CMV reactivation | |
| Cladiribine | Depends on protocol | Monitor LFT, RFT, Irradiated blood products | |
| Cytarabine | Depends on protocol | Hepatic correction, Monitor CBC, LFT, RFT. Avoid if ANC <1000/cmm and PL <50,000. W/F Cytosine fever, rash For HIDac- Use steroid eye drops, W/E cerebellartoxicity, oral/anal inflammation |
Vinca alkaloids:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Vincristine | Depends on protocol | Maximum dose 2mg, Hepatic correction, W/F- Peripheral neuropathy, constipation, Jaw pain, SIADH, Cranial nerve palsy. Accidental IT administration is lethal. | |
| Vinblastine | Depends on protocol |
Anthracyclines:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Doxorubicin (Adriamycin) | Depends on protocol | Start only if Echo- EF- >40%, Hepatic correction, Lifetime dose <550mg/m2, Monitor CBC, LFT, W/F- CCF, Arrythmia, Can cause red urine | |
| Daunorubicin | Depends on protocol | Start only if Echo- EF- >40%, Light protection of bottle and tubings, hepatic correction, renal correction, Life time dose <550mg/m2, Monitor RFT, LFT, Nail pigmentation, Can cause red urine | |
| Mitoxantrone | Depends on protocol | Start only if Echo- EF- >40%, Life time dose <140mg/m2, Monitor ANC |
Tyrosine kinase inhibitors: (Adverse effects common to all TKI- Rash, nausea, edema, fatigue, myalgias, arthralgias)
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Imatinib | 400mg- OD | Take with meals with large glass of water, Can cause Nausea, periorbitaledema, rash, myalgia, headache, bone pain, fluid retention, hair repigmentation, muscle cramps, diarrhea | |
| Nilotinib | 300mg- BD | Avoid food 2 hrs before and 1 hr after, W/F QTc prolongation, Hold if QTc>480msec. Monitor BP, as hypertension is common. | |
| Dasatinib | 100mg- OD for CML CP 70mg- BD- For Advanced CML disease | Avoid if patient has previous pleuro-pulmonary or pericardial diseases. Monitor BP, as hypertension is common. Causes QTc prolongation Can cause platelet dysfunction | |
| Bosutinib | 400mg- OD as first line and 500mg- OD as second line | Hematological toxicity: Hold if ANC <1000/cmm or PL count <50,000/cmm. Resume at same dose if recovery (ANC >1000/cmm and PL count >50,000) occurs within 1 week. If it takes longer time, restart at lower dose (300mg-OD). Hypertension is common. May cause pancreatitis | |
| Ponatinib | Start with 45mg- OD, Decrease dose to 15mg-OD once IS is <1%. (For CMP AP/BC: Continue 45mg/day) | Hematological toxicity: Hold if ANC <1,000/cmm or Platelet count <50,000/cmm and restart at dose of 300mg-OD once ANC >1500/cmm and platelet count >75,000/cmm. If same thing recurs, hold again till same time and restart at 10mg-OD. If same thing recurs, discontinue. G-CSF may be used if required. Discontinue if patient develops, arterial occlusive events/ heart failure/ symptomatic pancreatitis W/F Hypertension Avoid with strong CYP3A4 inhibitors | |
| Asciminib | Refer CML section |
Anti-myeloma medications:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Bortezomib | Depends on protocol | W/F Cytopenia, peripheral neuropathy, diarrhea, no green tea, Can cause hyperbilirubinemia, Aciclovir prophylaxis is must | |
| Carfilzomib | |||
| Lenalidomide | Depends on protocol | Severe teratogenicity (phacomalia)- Avoid pregnancy (Use 2 contraceptive methods) Renal correction, Monitor LFT, RFT, CBC. Hold if ANC <500, PL<30,000. Reatsrt at decreased dose Aspirin as DVT prophylaxis | |
| Thalidomide | Depends on protocol | Severe teratogenicity (phacomalia)- Avoid pregnancy (Use 2 contraceptive methods) Take with water 1 hr after food at night. Monitor CBC- Hold of ANC<750 W/F- Somnolense, peripheral neuropathy, constipation, DVT/PE Aspirin to be given as DVT prophylaxis |
Monoclonal antibodies:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Rituximab | Depends on protocol | Can cause serious allergic reactions, Premedicate with Methylprednisolone, Avil and Paracetamol. First 100mg over 1hr, if no reaction rest over 4-5hrs. Monitor during infusion Check HBsAg status- If positive start HBV treatment, Monitor HBV DNA once in 2 months | |
| Obinutuzumab | 1000mg- IV. | (Premedicate with Avil and hydrocort, Give 100mg in 100ml NS over 1hr, if no reaction, add remaining 900mg in 250ml NS and infuse over 2 hrs) In case of infusion related reaction: If mild, hold infusion, treat and resume. If severe, Permanently discontinue. Common SE: Tumor lysis syndrome, Cytopenia Check HBsAg status- If positive start HBV treatment, Monitor HBV DNA once in 2 months |
Hypomethylating agents:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Decitabine | Depends on protocol | Monitor CBC, W/H or decrease dose if cytopenia, monitor K, Mg, Na, LFT, RFT | |
| 5-Azacytidine | Depends on protocol | Monitor CBC, W/H or decrease dose if cytopenia, monitor K, Mg, Na, LFT, RFT |
Others:
Name | Dose (Adults) | Dose (Paediatric) | Precautions |
| Etoposide | Depends on protocol | Monitor CBC, LFT, RFT, W/F- Hypotension (slow down infusion rate), W/F Peripheral neuropathy, Hold if ANC<500, PL<50k High toxicity in patients with low albumin | |
| Bleomycin | Depends on protocol | Renal correction, Start only if PFT is normal, Can cause interstitial pneumonitis followed by pulmonary fibrosis, Lifetime dose <400units/m2, W/F- Rash, arrythmia, Contraindicated with Brentuximab No marrow toxicity | |
| Hydroxyurea | Depends on protocol | Titrate dose base on ANC, Monitor RFT, Stop if TLC <2k/ PL<1lac, W/F skin ulcer | |
| L-Asparaginase | Depends on protocol | Monitor CBC, LFT, BSL, If VTE, further doses must be administered under cover of therapeutic/ prophylactic anticoagulation. | |
| Carboplatin | Depends on protocol | Renal correction, Cytopenia, W/F- Ototoxicity, neuropathy | |
| Cisplatin | Needs hyper hydration. Monitor renal functions | ||
| Gemcitabine | Depends on protocol | Monitor LFT, CBC, RFT, W/F- Hematuria, Contraindicated with radiotherapy | |
| ATRA | Depends on protocol | W/F- Differentiation syndrome (Management in APML section), Pseudotumor cerebri Causes dry skin, cheilitis, arthralgia | |
| Arsenic trioxide | Depends on protocol | W/F- Differentiation syndrome (Management in APML section), Monitor ECG for QTc prolongation (<500msec), Correct hypokalaemia and hypomagnesemia Contraindicated along with artemether, cisapride, erythromycin, nilotinib, amiodarone, amitriptyline, azithromycin, azole antifungals, quinolones | |
| Ibrutinib | CLL- 420mg-OD-PO MCL- 560mg-OD-PO | W/F Initial lymphocytosis (nothing needs to be done), Bleeding (Mech not known), New onset atrial fibrillation, hypertension Avoid with CYP3A inducers/inhibitors | |
| Acalabrutinib | 100mg-BD-PO | No dose changes necessary for mild-moderate renal/ hepatic impairment Common SE (hold treatment as necessary): Anemia, thrombocytopenia, neutropenia, headache, diarrhea, fatigue, myalgia, bruising/ serious hemorrhage, nausea, constipation Hold 3-7 days prior to surgery Consider anti-infective prophylaxis in view of serious infective complications W/F Atrial fibrillation Avoid co-administration of CYP3A inhibitors and PPI/ other antacids. | |
| Ruxolitinib | Start with 5mg BD and then gradually increase to 20mg- BD (Increase dose once in 4 weeks) | Needs dose adjustments for hematological toxicity. Monitor lipid levels monthly and treatment of hyperlipidemia if seen. Needs renal and hepatic dose correction. High risk of opportunistic infections including TB, VZV and hepatitis B reactivation. Discontinue if there no response or improvement (<50% decrease in spleen size/ persistent symptoms) after 6 months of therapy. When discontinuing, taper and stop. | |
| Luspatercept | 1mg/kg- SC- Once in 3 weeks | If still transfusion dependent after 2 doses, increase dose to 1.33 mg/kg- SC- Once in 3 weeks If still transfusion dependent after 2 doses, increase dose to 1.75 mg/kg- SC- Once in 3 weeks If still transfusion dependent after 3 doses- Stop Hold if Hb >11gm/dL If rise in Hb is >2gm/dL within 3 weeks reduce dose.
Stop if severe hypersensitivity reactions. Avoid in pregnant/ during breast feeding. No dose adjustments needed for renal/ hepatic impairment Common side effects: Rise in bilirubin, transaminitis, headache, musculoskeletal/ bone pain, arthralgia, fatigue, abdominal pain, diarrhoea, diszziness, hypertension | |
| Brentuximab vedotin | Upfront (with AVD): 1.2mg/Kg-IV-Once in 2 weeks Relapsed HL/ Post ASCT/ALCL consolidation: 1.8mg/Kg-IV- Once in 3 weeks | Avoid if creat clearance <30mL/min. More than this, use same dose. Avoid if Child Pugh B or C. For Child Pugh A, use same dose. Neuropathy: Grade 2/3- Hold until improvement and restart at same dose. Grade 4- Discontinue Neutropenia: Use G-CSF, Hold until recovery. If recurrent, discontinue. Contraindicated with bleomycin (Severe pulmonary toxicity) Common SE: Anemia, neutropenia, peripheral neuropathy, constipation, vomiting, diarrhea, pyrexia, weight loss, stomatitis, abdominal pain, back ache, rashes | |
| Venetoclax | Depends on Indication: Usually, Start with 50mg- PO-OD with meals and try to increase the dose up to 400mg-OD | If used with posaconazole or other CYP3A4 inhibitor, reduce dose from 400mg to 70mg. For mild to moderate hepatic/ renal impairment, no dose adjustments are necessary. Cytopenia is the most common side effect. Need to decrease the dose as per following protocol.
|
An Initiative of
Veenadhare Edutech Private Limited
1299, 2nd Floor, Shanta Nivas,
Beside Hotel Swan Inn, Off J.M.Road, Shivajinagar
Pune - 411005
Maharashtra – India
howitreat.in
CIN: U85190PN2022PTC210569
Email: admin@howitreat.in
Disclaimer: Information provided on this website is only for medical education purposes and not intended as medical advice. Although authors have made every effort to provide up-to-date information, the recommendations should not be considered standard of care. Responsibility for patient care resides with the doctors on the basis of their professional license, experience, and knowledge of the individual patient. For full prescribing information, including indications, contraindications, warnings, precautions, and adverse effects, please refer to the approved product label. Neither the authors nor publisher shall be liable or responsible for any loss or adverse effects allegedly arising from any information or suggestion on this website. This website is written for use of healthcare professionals only; hence person other than healthcare workers is advised to refrain from reading the content of this website.