Case Study 5

For each question, choose the answer you think is correct. Answers are provided at the end of the page.
​​​​​​​​​​​​​​​​​​​​​​​​D.G. is a 76-year-old female, diagnosed with Stage IVA diffuse large B-cell lymphoma (DLBCL), scheduled to receive 6 cycles of LYCHOPR. 

She has a history of breast cancer treated 15 years ago with 4 cycles of doxorubicin, an anthracycline drug, and cyclophosphamide (BRAJAC at full doses with BSA 1.58 m2), which she tolerated well. 

An echocardiogram (ECHO) performed last month showed a normal left ventricular ejection fraction (LVEF) of 60%.

Weight: 52 kg Height: 159 cm 

Lab results (24 hours prior to first LYCHOPR treatment)
​WBC                    6.1 (x 109/L)
ANC                     3.7 (x 109/L)
Platelets           175 (x 109/L)
Lymphocytes   1.5 (x 109/L)
Creatinine          77 µmol/L

Bilirubin                             12 µmol/L
ALT                                        31 U/L
LDH                                      110 U/L
HBsAg                                 Non-reactive 
(Hep B Interpretation - No  evidence of active HBV infection)
HBCoreAb                        Reactive
HBsAb                                  >1000 IU/L

1. Based on the LYCHOPR protocol summary and D.G.’s prior cancer treatment history, which of the following is the most appropriate approach to her treatment plan? Select ONE.

  1. Doxorubicin is contraindicated because she previously received it for breast cancer treatment 
  2. Previous treatment can be disregarded because it was administered 15 years ago, and sufficient time has elapsed.
  3. Previous treatment was for a different cancer type; therefore, cumulative anthracycline dose is not a concern.
  4. She may receive more doxorubicin along with continued cardiac monitoring since her LVEF is normal. 
  5. She may receive more doxorubicin for Cycle 1 only with the addition of dexrazoxane as a cardioprotective agent
  6. Doxorubicin should be replaced with etoposide 50 mg/m2 IV on Day 1 and 100 mg/m2 PO on Days 2 and 3

​2. D.G. should be monitored in Cycle 1 for hypersensitivity reactions to which drug during administration? Select ONE.

  1. vincristine
  2. prednisone 
  3. etoposide 
  4. rituximab

3. Which of the following best describes the doses of LYCHOPR that D.G. should receive for her first cycle? Select ONE.

  1. Cyclophosphamide 855 mg, DOXOrubicin 57 mg, vinCRIStine 2.1 mg, riTUXimab 600 mg, and predniSONE 75 mg PO daily × 5 days
  2. Cyclophosphamide 855 mg, DOXOrubicin 57 mg, vinCRIStine 2.1 mg, riTUXimab 1400 mg, and predniSONE 75 mg PO daily × 5 days
  3. Cyclophosphamide 1140 mg, DOXOrubicin 76 mg, vinCRIStine 2.1 mg, riTUXimab 570 mg, and predniSONE 75 mg PO daily × 5 days
  4. Cyclophosphamide 855 mg, etoposide 57 mg, vinCRIStine 1.6 mg, riTUXimab 570 mg, predniSONE 75 mg PO daily × 5 days
  5. Cyclophosphamide 855 mg, etoposide 57 mg, vinCRIStine 2.1 mg, riTUXimab 600 mg, predniSONE 50 mg PO daily × 5 days

​4. D.G. will be receiving the CHOP portion of the protocol on a different day than rituximab. Which drugs does she have to receive first? How much time can elapse between the CHOP and rituximab treatment? Select ONE.

  1. Treatment can be scheduled at the patient’s convenience, as long as CHOP is started on the first day and the prednisone is taken in the morning before receiving rituximab
  2. The rituximab should be given on Day 1 and the CHOP portion can be given on Day 2 or 3
  3. Th​e CHOP portion should be given on Day 1 and the rituximab within 48 hours of Day 1 
  4. The CHOP portion should be given on Day 1 and the rituximab may be given on Day 1 or Day 2, but no later than 72 hours after CHOP. The patient must start her prednisone on Day 1, and must make sure a dose of prednisone is taken in the morning before receiving rituximab

​5. Which of the following supportive care medications does D.G. require for Day 1 based on her diagnosis, treatment protocol and blood test report? Select ONE.

  1. dexamethasone, hydrocortisone and diphenhydramine with prn prochlorperazine
  2. dexamethasone, ondansetron, and aprepitant with prn prochlorperazine
  3. entecavir for duration of cancer treatment and 18 months afterwards
  4. 2 and 3 only
  5. All of the above

​6. D.G. tolerated Cycle 1 rituximab without any issues. What should her rituximab dose be for Cycle 2?

  1. riTUXimab 600 mg IV over 90 minutes on Day 1
  2. riTUXimab 1400 mg subcutaneously over 5 minutes on Day 1
  3. riTUXimab 375 mg/m2 IV over 90 minutes on Day 1
  4. riTUXimab 570 mg IV over 90 minutes on Day 1
  5. rituximab 1700 mg subcutaneously over 5 minutes on Day 1

​7. Based on the blood test report prior to Cycle 5, which of the following interventions may be appropriate for D.G.?

Lab results 

      ​WBC                         2.1 (x 109/L)              Bilirubin    25 µmol/L
      ANC                          1.1 (x 109/L)              ALT               35 U/L
      Platelets                 50 (x 109/L)
      Hemoglobin          69 g/L

  1. platelet transfusion to maintain platelets greater than 120 x 109/L
  2. filgrastim 300 mcg starting on Day 7 of Cycle 5 and continue for 5 days 
  3. RBC transfusion to maintain hemoglobin above 70 g/L
  4. Omit doxorubicin and add cyclophosphamide 350 mg/m2 to the dose already planned
  5. None of the above

Answer 1
​The correct answer is 4. 

Rationale: The LYCHOPR protocol “Precautions” section recommends cardiac assessment once a cumulative doxorubicin dose of 300 mg/m2 is reached. Anthracycline cardiotoxicity is cumulative and lifelong; therefore, total lifetime exposure across all treatment settings must be tracked. Patient tolerance can vary, with some developing heart failure at doses below 300 mg/m2, while others tolerate doses exceeding 1000 mg/m2. See Clinical Pharmacy Guide, Appendix B: Guidelines for Anthracycline Monitoring Thresholds.

Based on prior BRAJAC treatment (doxorubicin 60 mg/m2x 4 cycles), D.G. received an estimated cumulative dose of 240 mg/m2 previously (see below). Cardiac assessment was already performed in anticipation of exceeding the anthracycline monitoring threshold. Patients at higher risk may also be referred to cardio-oncology.

Anthracycline Lifetime Cumulative Dose (LCD) Calculation
​Prior exposure
BRAJAC doxorubicin = 60 mg/m2 per cycle x 4 cycles = 240 mg/m2

Remaining dose before monitoring threshold
Recommended monitoring threshold (300 mg/m2) – dose already received = amount remaining: 300 mg/m2 – 240 mg/m2 = 60 mg/m2 

Current regimen dose
LYCHOPR doxorubicin = 50 mg/m2 per cycle

Number of cycles before monitoring threshold
Dose remaining ÷ dose per cycle: 60 mg/m2 ÷ 50 mg/m2 = 1.2 cycles

Given her normal LVEF, the most appropriate approach is to proceed with doxorubicin while continuing cardiac monitoring at the physician’s discretion. 

According to the BC Cancer Pharmacy FAQ Dexrazoxane use for anthracycline cardiotoxicity prevention​, dexrazoxane may be considered once the cumulative dose reaches 300 mg/m2 (~Cycle #2 of LYCHOPR) if she continues to benefit from therapy. However, if she develops symptomatic heart failure or reduced LVEF, doxorubicin should be switched to etoposide for the remainder of her treatment.

Answer 2

The correct answer is 4.​

Rationale:  Under the LYCHOPR protocol “Precautions” section, point 4 indicates the need to monitor for hypersensitivity reactions to both etoposide and rituximab​. However, this particular patient is receiving rituximab and doxorubicin (not etoposide in place of doxorubicin), so rituximab is the only drug monitored for hypersensitivity. This does not preclude the fact that the patient could have hypersensitivity reactions to the other drugs in this protocol, but a higher percentage of patients react to rituximab and thus it is anticipated and monitored for.

Answer 3
The correct answer is 1.

Rationale:
 
Based on the LYCHOPR protocol “Dose Modifications” section, doxorubicin and cyclophosphamide doses in Cycle 1 should be reduced to 75% for patients greater than 75 years old. The doses can be escalated to 100% in subsequent cycles, depending on the patient’s tolerance to the reduced dose.  

The LYCHOPR protocol “Treatment” section indicates that the first dose of rituximab (Cycle 1) must be administered by IV infusion since infusion-related (hypersensitivity) reaction risk is highest with the first dose. Premedication with antihistamine and antipyretic is routinely used, and rituximab IV is infused using a step-wise titration starting at a slower rate.

Doses are calculated as follows
​​Cyclophosphamide = 750 mg/m2 x 0.75 x 1.52 m2  = 855 mg
Doxorubicin = 50 mg/m2 x 0.75 x 1.52 m2  = 57 mg
Vincristine = 1.4 mg/m2 x 1.52 m2  = 2.1 mg 
Rituximab = 375 mg/m2 x 1.52 m2  = 570 mg  (This rituximab dose will need to be dose banded per Provincial Systemic Therapy Policy III-190. Based on the rituximab dose banding table in LYCHOPR, the dose should be 600 mg.)
Prednisone = 45 mg/m2 x 1.52 m2 = 68.4 mg (rounded to nearest 25 mg = 75 mg) daily x 5 days

Answer 4

​The correct​​ answer is 4.

Ration​​ale: ​The LYCHOPR protocol states that cyclophosphamide, doxorubicin, vincristine and prednisone (the “CHOP” portion of the protocol) are to be given on Day 1. Rituximab may be given on either Day 1 or 2 whenever possible, but no later than 72 hours after “CHOP”, with the daily dose of prednisone taken on the morning of the rituximab day (i.e., before the rituximab administration to help prevent infusion-related reactions and cytokine release syndrome). Refer to your site practices. 

It is typically given on Day 2 for Cycle 1 at BC Cancer. The first day of treatment is considered Day 1 of Cycle 1.

Answer 5

​The correct answer is ​4.

Rationale: The “Premedications” section of the LYCHOPR protocol states the CHOP portion of this protocol is considered highly emetogenic chemotherapy. Based on D.G.’s risk factors (age, gender, previous chemotherapy tolerance) and financial drug coverage, an alternate antiemetic regimen may be selected. Refer to the LYCHOPR pre-printed order (PPPO) “Premedications” section for options. Based on symptom control, antiemetic therapy may be modified as the treatment progresses.

The LYCHOPR PPPO indicates that hydrocortisone 100 mg IV and/or diphenhydramine 50 mg IV may be given as premedication prior to etoposide. This is generally reserved for patients who have previously experienced a hypersensitivity reaction to etoposide. This type of reaction is rare with oral etoposide capsules; however, the prescriber must be consulted to confirm whether the patient will receive any future IV doses of etoposide. For all subsequent IV doses, patients who have experienced a prior reaction should be pre-medicated with diphenhydramine and hydrocortisone. In cases of more severe hypersensitivity reactions, etoposide may be omitted, or a switch to Special Access Drug (SAP) etoposide phosphate may be considered.     

According to the BC Cancer supportive care protocol SCHBV, when a patient is hepatitis B surface antigen negative and hepatitis B core antibody positive and receiving B-cell depleting therapy, such as rituximab, they are at very high risk for HBV reactivation and should start entecavir prior to immunosuppressive therapy, continue throughout the duration of therapy, and for 18 months afterward. Monitoring for HBV DNA (viral load) and ALT is continued q 3 monthly for at least 12 months after stopping the antiviral.

Answer 6
​The correct answer is 2.

Rationale: According to the “Treatment” section of the LYCHOPR protocol: If the patient tolerates Cycle 1 IV infusion without any severe reactions requiring early termination, the subsequent doses can be given by subcutaneous (SC) administration. Check the patient chart for documentation. 

The SC dosing is a fixed dose 1400 mg SC for this protocol.

Answer 7

​The correct answer is 3.

Rationale: According to the “Dose Modifications” Hematological section of the LYCHOPR protocol, RBC transfusion support should be considered in individuals that have an expected hemoglobin nadir below 70 to 80 g/L and D.G.’s current hemoglobin is 69 g/L. 

The protocol also mentions that platelet transfusions are considered to keep platelets greater than 20 (x 109/L), and filgrastim support is required in patients with ANC of less than 0.8 (x 109/L). 

There are hepatic dose modifications as well for doxorubicin and vincristine. For example, if bilirubin is greater than 85 µmol/L, doxorubicin should be omitted and cyclophosphamide 350 mg/m2 should be added to the dose already planned.

​​​​​​​​​​​​​​​​​
The correct answer is 1

Rationale:

Based on the LYCHOPR protocol 'Dose Modifications' section, DOXOrubicin and cyclophosphamide doses in Cycle 1 should be reduced to 75% for patients greater than 75 years old. The doses can be escalated to 100% in subsequent cycles, depending on the patient’s tolerance to the reduced dose. Doses are calculated as follows:

Cyclophosphamide dose = 750 mg/m2 x 0.75 x 1.52 m2
= 855 mg

DOXOrubicin dose = 50 mg/m2 x 0.75 x 1.52 m2
= 57 mg

VinCRIStine dose = 1.4 mg/m2 x 1.52 m2
= 2.1 mg

RiTUXimab dose = 375 mg/m2 x 1.52 m2
= 570 mg

Prednisone dose = 45 mg/m2 x 1.52 m2
= 68.4 mg (rounded to nearest 25 mg = 75 mg) daily x 5 days

The correct answer is 4.

Rationale: The LYCHOPR protocol states that cyclophosphamide, DOXOrubicin, vinCRIStine and predniSONE (the 'CHOP' portion of the protocol) are to be given on day 1. RiTUXimab may be given on either day 1 or 2 whenever possible, but no later than 72 hours after 'CHOP' with the daily dose of predniSONE taken on the morning of the riTUXimab day (i.e. before the riTUXimab administration). Refer to your site practices. It is typically given on Day 2 for Cycle 1 at BC Cancer.

​The correct answer is 4.

Rationale: Under the LYCHOPR protocol "Precautions" section, point 4 indicates the need to monitor for hypersensitivity reactions to both etoposide and riTUXimab. However, this particular patient is receiving riTUXimab and DOXOrubicin, (not etoposide in place of DOXOrubicin), so riTUXimab is the only drug monitored for hypersensitivity. This does not preclude the fact that the patient could have hypersensitivity reactions to the other drugs in this protocol, but a higher percentage of patients react to riTUXimab and thus it is anticipated and monitored for.