What are the signs and symptoms of Non-Hodgkin’s Lymphoma (NHL)?
“B” Symptoms (20%) - Fever, Weight loss, Drenching night sweats. Lymphadenopathy (65%) - Peripheral (most commonly cervical), 20% mediastinal. Fatigue, pruritus, malaise. Bone marrow involvement (33%). Extranodal
What is use in the Ann Arbor Staging of Non-Hodgkin’s Lymphoma (NHL)?
“B” symptoms. Bulky disease (tumor mass > 10cm in greatest diameter, localized (stage I or II) w/ bulky disease are treated as advanced disease (stage III or IV)
What are used to categorize patients in the different risk categories for Non-Hodgkin’s Lymphoma (NHL)?
Age > 60. Stage III or IV. >2 extranodal sites. Performance status > 2. LDH > norma
What are the characteristics of Low grade NHL?
Cure if rare. Median overall survival (5-8 years). Prognosis depends on (age, bulk of disease)
What are the different treatment options for Low Grade NHL?
Observation. Radiation for localized. Chemotherapy for disseminated
What are the ADRs with Prednisone?
Insomnia (take dose QAM). Hyperglycemia. Increase appetite. Indigestion, gastritis
What dosage forms does Prednisone come in?
Oral solution: 1mg/mL. Concentrate oral solution (5mg/mL). Tablet: 1, 2.5, 5, 10, 20, 50mg. Take with food
What are the ADRs with Cyclophosphamide (Cytoxan)?
Hemorrhaghic cystitis (at high dose) - MESNA, hydration. Alopecia, Myelosuppression (leukopenia), infertility
What is the Emetogenicity like for Cyclophosphamide (Cytoxan)?
High
What is the dose adjustment like for Cyclophosphamide (Cytoxan)?
Hepatic: no official recommendation. Renal < 10: 75% dose
What dosage form does Cyclophosphamide (Cytoxan) come in?
Injectable, oral tablet 25, 50mg
What is Fludarabine (Fludara) indicated for?
CLL (NHL not FDA approved, but commonly used)
What are the ADRs with Fludarabine (Fludara)?
Myelosuppression (leukopenia, thrombocytopenia). Increased risk for opportunistic infection d/t decreased CD4 counts, pneumonia. Fever, fatigue, edema
What is the Emetogenicity like for Fludarabine (Fludara)?
Very low
What is dose adjustment like for Fludarabine (Fludara)?
CrCl 30-70: 20% dose reduction. CrCl < 30: not recommended
How is Fludarabine (Fludara) administered?
Infusion over 30-60 minutes
What are the ADRs with Mitoxantrone (Novantrone)?
Discoloration of urine, saliva, tears, and sweat (blue-green for 24 hrs post). Cardiotoxicity (CHF, decreased cardiac function (LVEF)
What is the Emetogenicity like for Mitoxantrone (Novantrone)?
Moderate
What is the dose adjustment like for Mitoxantrone (Novantrone)?
Hepatic (no official recommendations). T.bili 1.5-3.0: 50% dose reduction. T.bili > 3.0: 75% dose reduction
What is a caution with Mitoxantrone (Novantrone) use?
Vesicant (management): DMSO, cold. Classified as an irritant
What is Chlorambucil (Leukeran) used for?
CLL, HD, NHL
What are the ADRs with Chlorambucil (Leukeran)?
Rash, myelosuppression (DLT). Transient increase in LFTs, hyperuricemia. Less common: hepatotoxicity, seizure, drug fever, pulmonary fibrosis
What is the Emetogenicity of Chlorambucil (Leukeran)?
Very low
How should Chlorambucil (Leukeran) be taken?
On empty stomach. BA decreased by 10-20% when taken with food
What are the treatment options for Aggressive NHL?
Localized: chemo +/- radiation. Disseminated: combination chemotherapy. R-CHOP: 1st line
What does R-CHOP stand for?
R: Rituximab (Rituxan). C: Cyclophosphamide (Cytoxan). H: Hydroxyl Daunorubicin. O: Vincristine (Oncovin). P: Prednisone
How is Rituximan (Rituxan) dosed in R-CHOP?
375mg/m2 IVPB day 1
How is Cyclophosphamide (Cytoxan) dosed in R-CHOP?
750mg/m2 IVPB day 3 (or day 1)
How is Hydroxyl Daunorubicin dosed in R-CHOP?
50mg/m2 IVP day 3 (or day 1)
How is Vincristine (Oncovin) dosed in R-CHOP?
1.4mg/m2 (max 2mg) day 3 (or day 1)
How is Prednisonse dosed in R-CHOP?
100mg/day PO days 3-7 (or days 1-5)
How often is R-CHOP repeated?
Repeat cycle every 21 days
What is the MOA of Rituximab (Rituxan)?
Monoclonal antibody. Anti-CD20. Chimeric (mouse/human)
What is Rituximab (Rituxan) used for?
NHL, RA, CLL
What are the infusion related reactions with Rituximab (Rituxan)?
Fever, chills/rigors, angioedema, flushing, HTN. Can premedicate with APAP
What is a BBW for Rituximab (Rituxan)?
Tumor Lysis Syndrome (high tumor burden (usually with 1st dose)). Fatal infusion reaction
How is Rituximab (Rituxan) prepared?
In D5W or NS, final concentartino 1-4mg/mL
What are the ADRs with Doxorubicin (Adriamycin)?
Myelosuppressive (Leukopenia). Urine/saliva/tear discoloration - red/orange. Cardiotoxicity
What is the Emetogenicity like with Doxorubicin (Adriamycin)?
Dose dependent. 20-60mg: moderate
What does Doxorubicin (Adriamycin) need to be dose adjusted?
AST/ALT 2-3x ULN: 75% of dose. >3x or T.bili 1.2-3: 50% of dose. T.bili 3.1-5: 25% of dose
What caution should be taken with Doxorubicin (Adriamycin)?
Vesicant (management): DMSO or Totect, cold
What are the ADRs with Vincristine (Oncovin)?
Peripheral neuropathy (DLT). Constipation (DLT)
What is Vesicant management like for Vincristine (Oncovin)?
Hyaluronidase (Amphadase, Wydase, Vitrase). Warm preferred over cold
When does Vincristine (Oncovin) required dose adjustment?
Hepatic
What is a warning with Vincristine (Oncovin)?
DO NOT remove covering until the moment of injection. For intravenous use only. FATAL if given intrathecally
What are the ADRs with Etoposide (Toposar, VePesid) - salvage therapy?
Hypotension if infused too rapidly. Myelosuppression (leukopenia > thrombocytopenia). Alopecia, asthenia, fever
What is the Emetogenicity with Etoposide (Toposar, VePesid)?
Mild
What does stability of Etoposide (Toposar, VePesid) depend on?
Concentration dependent
When does Etoposide (Toposar, VePesid) need dose adjustment?
Renal, Hepatic
What do you need to do when administering Etoposide (Toposar, VePesid)?
Use in-line filter with high doses d/t high likelihood of precipitation
What are the ADRs with Cytarabine (Cytosar, ARA-C) - salvage therepy?
Ocurlar (use opthalmic corticosteroids - Prednisolong (Pred-Forte)). Fever, rash, hyperuricemia. Myelosuppression. Acute increase LFT, mild jaundice. Neurotoxicity - high dose
What is the Emetogenicity of Cytarabine (Cytosar, ARA-C)?
High
What are the ADRs with Cisplatin (CDDP, Platinol)?
Neurotoxicity: Peripheral neurotoxicity is dose- and duration-dependent. Myelosuppression. Nephrotoxicity, ototoxicity
What is the Emetogenicity like for Cisplatin (CDDP, Platinol)?
High
What is the stability of Cisplatin (CDDP, Platinol) like?
Stable in saline only
When does Cisplatin (CDDP, Platinol) need dose adjustment?
Renal only
What is done for Cisplatin (CDDP, Platinol) as a vesicant?
In high dose. Sodium thiosulfate and cold
What needs to be monitored while on Cisplatin (CDDP, Platinol)?
Renal function, electrolytes, CBC, hearing test, neuro exam
What are the ADRs with Ifosfamide (IFEX) - salvage therapy?
Alopecia. Confusion, hallucination (avoid with BZD). Myelosuppression. Metabolic acidosis. Hemorrhagic cystitis, hematuria (ALWAYS give Mesna)
What is the Emetogenicity of Ifosfamide (IFEX)?
Moderate
What does Ifosfamide (IFEX) need dose adjustment?
Renal if significant impairment. Hepatic: 75% dose reduction if AST > 300 or T.bili < 3
What is the MOA of Mesna (Mesnex)?
Mesna oxidized to dimesna in blood. Reduced in the kidney back to mesna yielding a free thiol group. Binds to and inactivates acrolein
What are the ADRs with Carboplatin (Paraplatin)?
Myelosuppression (dose related and dose limiting)
What is the Emetogenicity of Carboplatin (Paraplatin)?
Moderate
What are the DDIs with Carboplatin (Paraplatin)?
Nephrotoxic drugs. AGs increase risk of ototoxicity
What are the ADRs with Bendamustine (Treanda)?
Myelosuppression (DLT), rash, HA, increased bilirubin, peripheral edema, TLS
What is the stability of Bendamustine (Treanda) like?
Concentration dependent. Stable in NS
What should be administered before Bendamustine (Treanda) use?
Premedicate to prevent hypersensitivity (APAP, antihistamine +/- corticosteroid)
What is the pathogenesis of Hodgkin’s Disease (HD)?
Bimodal age distribution (15-45 and > 50. More common in caucasian). Presence of Reed-Sternberg (large size, binucleated, cellular origin characteristic of macrophage and lymphocyte)
What is Stage I HD?
Involvement of single lymph node region or single extralymphatic site
What is Stage II HD?
Involvement of two or more lymph node regions on same side of diaphragm; may include localized extralymphatic involvement on same side of diaphragm
What is Stage III HD?
Involvement of lymph node regions on both sides of diaphragm; may include spleen or localized extranodal disease
What is Stage IV HD?
Diffuse extra-lymphatic disease (e.g. in liver, bone marrow, lung, skin)
What is the treatment strategy for Stage IA or IIA HD (with favorable prognostic factors)?
Radiation. Radiation +/- chemotherapy
What is the treatment strategy for Stage IB or IIB HD (with bulky disease)?
Chemotherapy + Radiation. Combination chemotherapy
What is the treatment strategy for Stage III or IV HD?
Chemotherapy +/- radiation
What is the treatment strategy for HD relapse?
SCT (stem cell transplant). Salvage therapy
What is the gold standard treatment option for HD?
ABVD (used to be MOPP)
What does MOPP stand for?
M: Mechlorethamine (Mustargen). O: Vincristine (Oncovin). P: Procarbazine (Matulane). P: Prednisone
What does ABVD stand for?
A: Doxorubicin (Adriamycin). B: Bleomycin (Blenoxane). V: Vinblastine (Velban). D: Dacarbazine (DTIC). Days 1 and 15 every 28 days for 6-8 cycles
What needs to be done before Bleomycin (Blenoxane) administration?
Test dose. Monitor vital signs, wait 1 hr prior to giving dose
What are the ADRs to look out for with Bleomycin (Blenoxane)?
Pulmonary fibrosis (cough, dypsnea, increased toxicity with O2 treatment up to 1 year after). Monitor PFT. Acute frebrile reaction. Dermatological SE
What is the emetogenicity like for Bleomycin (Blenoxane)?
Very low
When does Bleomycin (Blenoxane) need to be dose adjusted?
Renal
What is the maximum cumulative lifetime dose of Bleomycin (Blenoxane)?
400 units
What are the ADRs with Vinblastine (Velban)?
Myelosuppressive (Leukopenia)
What is the Vesicant management for Vinblastine (Velban)?
Hyaluronidase (Amphadase, Wydase, Vitrase). Warm/cold
When does Vinblastine (Velban) need dose adjustment?
Hepatic
What is a warning with Vinblastine (Velban)?
DO NOT remove covering until the moment of injection. For intravenous use only. FATAL if given intrathecally
What are the ADRs with Dacarbazine (DTIC)?
Myelosuppressive. Irritant (possible vesicant). Infusion related reaction (painful, dexamethasone as premedication, hot pack)
What is the Emetogenicity of Dacarbazine (DTIC)?
High
How does MOPP compare to ABVD?
MOPP involved with more: Hematological toxicity, Infection risk, Neuropathy, Secondary leukemia, Infertility
What is the MOA of Brentuximab Vetodin (Adcetris)?
Antibody drug conjugate (Anti-CD30) with 3 components: 1) CD30-specific chimeric IgG1 antibody - cAC10. 2) Microtubule-disrupting agent - MMAE. 3) Protease cleavable dipeptide linker
What are the common ADRs with Brentuximab Vetodin (Adcetris)?
Rash, BMS, fatigue, peripheral neuropathy
What are the serious ADRs with Brentuximab Vetodin (Adcetris)?
Anaphylaxis, PML, pulmonary toxicity, SJS
What are the potentially fatal late complications of HD treatment?
Acute myelomonocytic leukemia. Diffuse, high-grade NHL. Solid tumors (mostly lung and breast cancer). Bacterial sepsis post splenectomy or spleen irradiation
What are the serious late complications of HD treatment?
Myocardial damage secondary to radiation/anthracyclines. Lung fibrosis d/t radiation plus bleomycin. Sterility in men and women. Growth abnormalities in children and adolescents. Opportunistic infections