Case Study 6

For each question, choose the answer you think is correct. Answers are provided at the end of the page.

​​T.E. is a 19-year-old male diagnosed with primary intracerebral lymphoma. He is admitted to your hospital to receive chemotherapy treatment using the LYHDMRTEM protocol.

Weight: 76 kg               Height: 160 cm

CrCl = 80 mL/min

Allergies: pollen, bee stings​

1. Which of the following statements best explains why T.E. is admitted to the hospital for his treatment?
  1. T.E. doesn’t need to be admitted; LYHDMRTEM​​​​​ chemotherapy can be administered in the outpatient setting 
  2. This is a potentially nephrotoxic regimen which requires administration in a hospital where rapid reporting of methotrexate levels is available 
  3. Due to the length of time for pre-hydration, treatment administration, and post-hydration, it is more convenient to treat T.E. as an inpatient 
  4. 2 and 3 above 
2. Which of the following statements best describes the purpose of leucovorin (folinic acid) in this treatment regimen?
  1. Leucovorin exhibits synergy with methotrexate and helps to increase the cytotoxic properties of methotrexate 
  2. Leucovorin has antineoplastic properties that are ideally suited for the treatment of intracerebral lymphoma 
  3. Leucovorin reduces the toxicity of methotrexate by rescuing normal cells from the toxic effect of methotrexate 
  4. Leucovorin is added to help maintain a urine pH above 7 
3. Which one of the following statements best describes the use of sodium bicarbonate in this treatment regimen?
  1. Sodium bicarbonate is utilized to alkalinize the urine, keeping the pH greater than or equal to 7 
  2. Sodium bicarbonate is administered in both oral and intravenous forms 
  3. Sodium bicarbonate therapy is initiated prior to chemotherapy and continues until methotrexate levels are less than 0.1 micromole/L
  4. All of the above 

4. What doses of methotrexate and rituximab should T.E. receive for Cycle 1?

  1. Methotrexate IV 8.832 g and riTUXimab IV 700 mg
  2. Methotrexate IV 8.832 g and riTUXimab IV 690 mg
  3. Methotrexate IV 14.72 g and riTUXimab IV 690 mg
  4. Methotrexate IV 8.832 g and riTUXimab SC 1400 mg

5. What medications should T.E. be receiving at Cycle 2 if Cycle 1 was well tolerated?

  1. ​Methotrexate IV, leucovorin IV q6h x 4 then PO, riTUXimab IV, temozolomide PO
  2. Methotrexate IV, leucovorin IV q6h x 4 then PO, riTUXimab SC, temozolomide PO
  3. Methotrexate IV, leucovorin PO, riTUXimab IV, temozolomide PO
  4. Methotrexate IV, leucovorin PO, riTUXimab SC, temozolomide PO

​6. What dose of temozolomide should T.E. receive?

  1. ​​​​275 mg
  2. 276 mg
  3. 280 mg
  4. 300 mg

Answer 1
​The correct answer is 4. 

Rationale: The LYHDMTXP protocol states that “Methotrexate must be given in a hospital where rapid reporting of methotrexate levels is available”. The protocol also requires a leucovorin infusion to begin exactly 24 hours after the beginning of the methotrexate infusion and to continue until methotrexate levels are below 0.1 micromol/L.  Pre- and post-methotrexate infusions of sodium bicarbonate and potassium are also required, which are more conveniently given if the patient is in a hospital. More information on the use of leucovorin with methotrexate may be found in Protectants [Clinical Pharmacy Guide – Module 5 – Supportive Care]. 

Answer 2
​​The correct answer is 3.

Rationale: Leucovorin reduces the toxicity of methotrexate by "rescuing" normal cells. In theory, it has been suggested that leucovorin has a preference for normal cells over certain tumour cells, due to a difference in their membrane transport mechanisms. This preference allows leucovorin to "rescue" normal cells from the toxic effects of methotrexate. More information on the use of leucovorin with methotrexate may be found in Protectants [Clinical Pharmacy Guide – Module 5 – Supportive Care]. 

Answer 3
​The correct answer is 4.

Rationale: The LYHDMTXP protocol states that patients must have creatinine clearance greater than 60 mL/min and vigorous IV hydration and urine alkalinization to maintain urine pH above 7. Details of pre- and post-hydration and urine alkalinization are in the “Treatment” section of the protocol. 

Answer 4
​The correct answer is 1. 

Rationale:  According to the “Treatment” section of LYHDMRTEM the methotrexate dose is prorated to GFR or CrCl. We will use the calculated creatinine clearance (CrCl) value. For GFR/CrCl between 60 mL/min and 84 mL/min, methotrexate dose should be 60% of the 8g/m2. Therefore, the dose is calculated as follows:

    BSA calculation  =  
​​
​​ = 1.84 m2 

Methotrexate dose = 8 g/m2 x 1.84 m2 x 0.6 = 8.832 g 
​Rituximab dose = 375 mg/m2 x 1.84 m2 = 690 mg
The rituximab dose follows dose banding using the table provided, dose should be rounded to 700 mg.

Answer 5
​The correct answer is 2. 

Rationale: Cycle 1 rituximab was well tolerated, and therefore, T.E. can receive his subsequent doses of rituximab in the subcutaneous formulation. 

Leucovorin is given exactly 24 hours after the start of the methotrexate infusion as IV q6h for 4 doses then PO until the methotrexate level is less than 0.1 micromol/L.

Temozolomide PO may be started at Cycle 2 per protocol. T.E. did not receive it with his first cycle, and it is given every other cycle.

Answer 6
​​The correct answer is 3. 

Rationale: Calculated temozolomide dose = 150 mg/m2 x 1.84 m2 = 276 mg
Temozolomide dose follows dose banding using the table provided, his dose should be rounded to 280 mg.
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