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CAV

Cancer Type: Breast, Gastrointestinal, Colorectal, Esophagus, Gastric / Stomach, Hepatobiliary / Liver / Bile Duct, Pancreas, Genitourinary, Bladder / Urothelial, Prostate, Gynecologic, Cervix, Endometrial, Ovary, Lung, Small Cell  Intent: Palliative
Regimen Category: Evidence-Informed
A - Regimen Name

CAV Regimen
Cyclophosphamide-ADRIAMYCIN ® (DOXOrubicin)-VinCRIStine


Disease Site
Breast
Gastrointestinal - Colorectal
Gastrointestinal - Esophagus
Gastrointestinal - Gastric / Stomach
Gastrointestinal - Hepatobiliary / Liver / Bile Duct
Gastrointestinal - Pancreas
Genitourinary - Bladder / Urothelial
Genitourinary - Prostate
Gynecologic - Cervix
Gynecologic - Endometrial
Gynecologic - Ovary
Lung - Small Cell

Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

For treatment of small cell carcinoma

 
B - Drug Regimen

cyclophosphamide
1000 mg /m² IV Day 1
DOXOrubicin
50 mg /m² IV Day 1
vinCRIStine
1.4 mg /m² IV (maximum 2 mg) Day 1
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

For a usual total of 6 cycles unless disease progression or unacceptable toxicity occurs

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

High

Other Supportive Care:

Also refer to CCO Antiemetic Summary

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. 

Dosage with toxicity

Hematologic Toxicities:  See general recommendations.
 
 
 
 
 
 
 
 
Neurotoxicity
 
Symptom
% usual Vincristine dose
Areflexia only
100 %
Abnormal buttoning, writing
67 %
Moderate motor neuropathy (± cranial)
Hold until recovery then reduce dose by 50%
Severe motor neuropathy
Omit



Hepatic Impairment

Bilirubin
Action
1. If Bilirubin 1-2 x ULN REDUCE Vincristine and Doxorubicin to 50% dose
2. If Bilirubin 2-4x ULN
REDUCE Vincristine and Doxorubicin to 25% dose
3. If Bilirubin > 4 x ULN
STOP treatment with Doxorubicin
 
Doxorubicin is contraindicated in patients with severe hepatic impairment, especially with elevated bilirubin. Consideration should be given to dose modification for patients with severe increases in transaminases; limited data exists on the use of doxorubicin in this setting as these patients are routinely excluded from clinical trials.

Renal Impairment

Cyclophosphamide: Dosage may be halved or interval increased by 50-100% if CrCl<0.3 mL/second.


 
F - Adverse Effects

Refer to cyclophosphamide, DOXOrubicin, vinCRIStine drug monograph(s) for additional details of adverse effects


Most Common Side Effects 

Less Common Side Effects, but may be
Severe or Life-Threatening

  • Nausea, vomiting
  • Increased LFTs
  • Alopecia
  • Anorexia, weight loss
  • Constipation
  • Diarrhea
  • Myelosuppression +/- infection, bleeding
  • Peripheral neuropathy (may be severe)
  • Rash
  • Arterial thromboembolism
  • Venous thromboembolism
  • Cardiotoxicity
  • GI perforation
  • Hypersensitivity
  • Pancreatitis
  • Pneumonitis
  • SIADH
  • Prolonged QTc
  • Tumour lysis syndrome
 
G - Interactions

Refer to cyclophosphamide, DOXOrubicin, vinCRIStine drug monograph(s) for additional details

 
H - Drug Administration and Special Precautions

Refer to cyclophosphamide, DOXOrubicin, vinCRIStine drug monograph(s) for additional details

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • Clinical toxicity assessment (including stomatitis, neurotoxicity, cardiotoxicity, local toxicity, cystitis)
  • CBC before each cycle
  • Baseline and regular liver function tests
  • Baseline and regular renal function tests and urinalysis
  • Cardiac examination especially with risk factors (including prior therapy with Epirubicin, Mitoxantrone, or other cardiotoxic drug), or a cumulative Doxorubicin dose of > 450 mg/ m2
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
1.5 hours
Pharmacy Workload (average time per visit)
36.054 minutes
Nursing Workload (average time per visit)
51.667 minutes
 
K - References

Greco FA, et al. Treatment of oat cell carcinoma of the lung: Complete remissions, acceptable complications and improved survival. Brit Med J, 1978; 2: 10-11.

von Pawel J, Schiller JH, Shepherd FA et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999;17(2):658-67. 

Prostate:

Amato RJ, Logothetis CJ, Hallinan R, et al.  Chemotherapy for small cell carcinoma of prostatic origin. J Urol 1992;147(3 Pt 2):935-7. 

López Cubillana P, Martínez Barba E, Prieto A, et al. Oat-cell carcinoma of the prostate. Diagnosis, prognosis and therapeutic implications. Urol Int. 2001;67(3):209-12.

Bladder:

Mukesh M, Cook N, Hollingdale AE, et al. Small cell carcinoma of the urinary bladder: a 15-year retrospective review of treatment and survival in the Anglian Cancer Network. BJU Int 2009;103(6):747-52.


PEBC Advice Documents or Guidelines

July 2019 Updated hyperlink to vincristine drug monograph


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.