Case Study 4

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

​L.Y. is a 42-year-old woman diagnosed with stage IIIc epithelial ovarian cancer. Her oncologist has suggested she receive paclitaxel and carboplatin, as per the GOOVCATX​ protocol.

Lab results:​

  • ANC 10.7 (x 109/L)
  • Platelets 398 (x 109/L) 
  • Creatinine 56 µmol/L, lab reported GFR 110 mL/,min

Weight: 73.4 kg; Height: 150 cm

1. What special precautions must be observed when preparing the paclitaxel dose?

  1. None required 
  2. Paclitaxel can react with DEHP in plasticized PVC equipment, so must be prepared using non-DEHP equipment 
  3. Paclitaxel can react with latex gloves 
  4. Paclitaxel requires a special diluent from the manufacturer 

2. GFR is used to determine the carboplatin dose. Based on L.Y.'s serum creatinine and weight, how does the calculated GFR estimate compare to the lab reported GFR estimate in this case? 

  1. The calculated GFR is less than the lab reported GFR in this case 
  2. The calculated GFR is more than the lab reported GFR in this case
  3. The calculated GFR is the same as the lab reported GFR in this case
  4. GFR cannot be calculated differently, only the lab reported GFR can be used for carboplatin dosing

3. Based on a starting AUC = 6, what dose of each drug can you expect for her first cycle of GOOVCATX?

  1. PACLitaxel 306 mg and CARBOplatin 900 mg 
  2. PACLitaxel 271 mg and CARBOplatin 900 mg 
  3. PACLitaxel 306 mg and CARBOplatin 954 mg 
  4. PACLitaxel 271 mg and CARBOplatin 954 mg 

4. L.Y. returns for her second cycle. Her weight is 67.3 kg, and her labs are: ANC = 3.9 (x 109/L), platelets = 128 (x 109/L), and creatinine = 63 µmol/L. The week prior to her second cycle, her platelets = 88 (x 109/L) and ANC = 0.9 (x 109/L). The physician has re-ordered the same doses as in Cycle 1. Are these doses appropriate? 

  1. No, according to the nadir taken the week prior, doses should be 80% of the previous cycle's dose 
  2. No, the patient has lost more than 5% of her body weight, enough that the doses for both drugs need to be modified 
  3. Yes, both doses are still correct despite the weight decrease and creatinine increase
  4. No, the carboplatin dose needs to be recalculated since creatinine has increased by more than 10% 

5. L.Y. experienced a Grade 2 (moderate) infusion-related  (hypersensitivity) reaction to paclitaxel during Cycle 2, presenting with flushing and back pain that resolved with supportive medications. She was able to complete the full doses of paclitaxel and carboplatin after symptom resolution and has otherwise tolerated treatment well. 

For Cycle 3, the provider orders increased premedication with dexamethasone (20 mg PO 12 h and 6 h pre-chemo), and a slower paclitaxel infusion rate with step-wise rate titration, per SCDRUGRX Subsequent Management guidelines. 

Which of the following are appropriate for Cycle 3? 

Select ALL that may apply.

  1. Reduce the paclitaxel dose by 25%
  2. Permanently discontinue paclitaxel
  3. Rechallenge with the full dose of paclitaxel
  4. Continue carboplatin without modification
  5. Omit carboplatin 


 

The correct answer is 3.

Rationale: Based on the GOOVCATX protocol "Dose Modifications, Hematology" section: if ANC is greater than or equal to 1.0 (x 109/L), and Platelets are greater than or equal to 100 (x 109/L), treat as per nadir if it is available. At nadir, ANC was 0.9 (x 109/L) and platelets were 88 (x 109/L) which means both PACLitaxel and CARBOplatin may be given at 100%. Note that this is 100% of the dose from the previous cycle that was calculated based on the previous GFR.

As per BC Cancer Policy III-10, the BSA calculated at Cycle 1 can be used for subsequent cycles. BSA recalculation for weight changes is warranted when weight changes are greater than 10%, or result in a dose variance outside 5%. In this case, the weight only decreased by 8.3%, and it would not change the dose by greater than 5%, so the PACLitaxel dose does not have to change as it was otherwise well tolerated.

As per the GOOVCATX protocol "Treatment" section: GFR should be recalculated if creatinine increases by greater than 20% or rises above the upper limit of normal. In this case, the small creatinine increase does not warrant a recalculation.

 

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Answer 1

​​​The correct answer is 2.

Rationale: Some drug solutions have the capacity to leach DEHP from PVC containers into the intravenous solution. PACLitaxel is one such drug. The Cancer Drug Manual's Chemotherapy Preparation and Stability Chart L to Z indicates that non-DEHP bags and tubing are to be used when preparing and administering paclitaxel. Refer to Non-DEHP Equipment [Clinical Pharmacy Guide – Module 4 - Parenteral Drug Delivery] for more information and the Compatibility of Drugs with IV Bags & Plastic Tubing (DEHP, PVC) FAQ.

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Answer 2
​The correct answer is 2.

Rationale: BC Cancer uses this modified Cockcroft-Gault equation to calculate creatinine clearance when dosing carboplatin. This calculation is built into BC Cancer electronic order dose calculators.

Calculated GFR =      N x (140 – age) x weight (kg)

                                           Serum creatinine (µmol/L)
                                                                                           Where N = 1.04 for females
         = 1.04 (140 – 42) x 73.4
56
= 133.6 mL/min
​

Calculated GFR (133.6 mL/min) is more than lab reported GFR (110 mL/min) in this case.

Either the Cockcroft-Gault calculated estimate of GFR or the lab reported estimate of GFR may be used to determine carboplatin dosing. However, if a directly measured GFR is available (e.g. a nuclear medicine Blood GFR test), this value should take precedence as it is the most accurate. It is important to use the same method of GFR estimation consistently throughout the treatment course. For example, if the lab reported GFR estimate is used initially, all subsequent dosing should also be based on the lab reported value rather than the Cockcroft-Gault estimate. Refer to Carboplatin Dosing [Clinical Pharmacy Guide – Module 3 - Renal Function Tests​ (PDF)] for more information.​

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Answer 3
​The correct answer is 1.

Rationale:  According to the GOOVCATX treatment plan, paclitaxel dosing is based on body surface area (BSA), while carboplatin dosing uses area under the curve (AUC) and GFR. The measured GFR or GFR estimated by the lab or by the Cockcroft-Gault calculation may be used. BC Cancer typically uses the Cockcroft-Gault calculated GFR estimate. Estimated GFR should be capped at 125 mL/min when calculating the initial carboplatin dose.
Mosteller equation (BSA in m2)  = 
=     
=             1.75 m2

Dose of PACLitaxel:    L.Y. can receive 175 mg/m2
           = 175 mg/m2   x   BSA  
= 175 mg/m2   x   1.75 m2 =   306.3 mg

Dose of CARBOplatin:   L.Y. can receive AUC 6, but the calculated GFR 136 mL/min estimate must be capped at 125 mL/min (per protocol)
= AUC x (GFR + 25)
= 6 x (125 + 25) =      900 mg
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Answer 4
​The correct answer is 3.

Rationale: Based on the GOOVCATX protocol “Dose Modifications, Hematology”:  If ANC greater than or equal to 1.0 (x 109/L) and Platelets greater than or equal to 100 (x 109/L), treat as per nadir if available. 

At nadir, ANC was 0.9 (x 109/L) and platelets were 88 (x 109/L) which means both paclitaxel and carboplatin may be given at 100% doses. 

Weight: As per BC Cancer Policy III-10, the body surface area (BSA) calculated at Cycle 1 can be used for subsequent cycles. Recalculation of BSA due to weight changes is considered only if the weight changes by more than 10% from baseline or most recent dose recalculation, or if the resulting dose would change by more than 5 %. In this case, the patient’s weight decreased by 8.3%, and it would not change the dose by greater than 5%, so the paclitaxel dose does not have to change as it was otherwise well tolerated.

Creatinine: As per the GOOVCATX protocol “Treatment” section: GFR should be recalculated if creatinine increases by greater than 20% or rises above the upper limit of normal. In this case, the small creatinine change does not warrant a carboplatin dose recalculation.
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Answer 5
​The correct answers are 3 and 4. 

The GOOVCATX protocol “Precautions” section points to the SCDRUGRX protocol which outlines immediate management of a hypersensitivity reaction to be used during the reaction, and also guidelines for subsequent cycle management. The GOOVCATX protocol and PPO already use routine H1 and H2 antagonist premedications. For Cycle 3, the provider chose to increase prophylactic steroid premedication (e.g., dexamethasone 20 mg PO 12 hours and 6 hours prior to paclitaxel) and use a slower start infusion rate to minimize risk and severity of another reaction. See SCDRUGRX PPO B for examples of modified infusion rates that may be used.  

Paclitaxel: These paclitaxel infusion-related reactions are not dose related; a dose reduction would not prevent recurrence. As the reaction was not severe, rechallenging with the full paclitaxel dose, along with appropriate prophylactic premedication, would be more appropriate than paclitaxel dose reduction or discontinuation. 

Carboplatin: (a platinum drug) can cause a different type of infusion-related (hypersensitivity) reaction, which is generally a true IgE-mediated allergic reaction, usually occurring in later cycles (Cycle 6+) after repeated exposure. Paclitaxel (a taxane drug) tends to cause non-IgE-mediated reactions that typically only occur in earlier cycles (Cycle 1 or 2). There is no known clinical risk of cross-reactivity between these two drugs and no need to omit carboplatin based on a paclitaxel reaction. Refer to the BCC Pharmacy Infusion Reactions (course code 6899) course on the PHSA LearningHub for more information.
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