What information should be included in a treatment protocol for cancer therapy?

From Cancer Guidelines Wiki


A treatment protocol provides details of the cancer therapy including chemotherapy, monoclonal antibodies, targeted therapy and related medicines to be administered on each day of the treatment cycle. A protocol also specifies guidelines and recommendations for administration, dose calculations, supportive therapy, monitoring parameters and criteria for dose modification.[1][2][3]

Treatment protocols for cancer chemotherapy support safe, evidence-based and cost-effective cancer treatment for all cancer patients. The use of detailed treatment protocols reduces non-evidence-based variation and standardises care, both of which are fundamental principles for optimising quality and safety in patient care.[1]

For purposes of this section the term "protocols" refers to all aspects of a treatment protocol including chemotherapy, biological therapy, targeted therapy and supportive medication.

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Evidence Summary

All systemic cancer therapy should be provided on the basis of a documented and referenced protocol, with dosing and schedule parameters as well as expected toxicities.[4][5][6]

The use of pre-documented protocols have been shown to reduce errors in prescribing.[6][7][2][3] Misinterpretations of published articles and errors occurring in original papers have led to fatal outcomes where the article has been used as a direct source for writing a chemotherapy order.[8]

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Consensus-based recommendationQuestion mark transparent.png

The protocol should come from an evidence-based, published source or validated standard reference source such as the Australian government’s eviQ Cancer Treatments online resource (Cancer Institute NSW) or Children’s Oncology Group (COG) wherever possible. The use of an abstract, which does not represent full results/analysis, should be discouraged as a direct source for writing a chemotherapy order unless an exceptional case arises (Carrington et al, 2010).

There should be a formalised process of initial review by a multidisciplinary team before a protocol is implemented into clinical practice (Carrington et al, 2010). The responsibilities of each member of the team in verifying the content of a protocol should be clearly defined.

Protocols agreed within an institution should be incorporated into an electronic program (e.g. an oncology information system or computerised prescribing system). A fully validated electronic prescribing system should be utilised for the prescribing of chemotherapy wherever available (National Chemotherapy Advisory Group, 2009). Where an electronic system is not available pre-printed prescriptions should be used.

Investigational medications, doses and administration schedules must be verified against a study protocol that has been approved by all relevant regulatory agencies and study sponsors. Any protocol amendments should be distributed immediately and an up-to-date copy of the study protocol should be readily available for reference (Goldspiel et al, 2015).

Requirements associated with the delivery of the protocol at a local level should be considered including availability of supportive services (e.g. pathology and the ability to manage expected adverse effects or events) (Carrington et al, 2010).

Protocols should be reviewed on a regular basis for currency and changes in practice (Carrington et al, 2010).

The format of the protocol should be: (Carrington et al, 2010)

  • Standardised and easily recognisable.
  • Clear and unambiguous.
  • Computer generated, not handwritten. Protocol templates stored electronically should be in read-only format to avoid unapproved alterations on the original. Access to the original protocol document should be restricted to authorised persons.
  • Clearly and fully referenced.
  • Authored, signed and dated with a review date, to allow everyone involved to identify and validate that they are using the most current version (Goldspiel et al, 2015).
  • Easily available to all staff. Web-based programs are useful in ensuring access to protocols for all staff including those outside the speciality or institution (e.g. emergency staff, GPs or patients). It must be ensured that the content is regularly maintained.

Practice pointQuestion mark transparent.png

The use of out-of-date protocols can compromise patient safety. Superseded protocols should be archived (not deleted) and only be accessible to a limited number of senior staff. It is recognised that older protocols may be useful as a reference source or for educational purposes.

Facilities should consider convening a regular review meeting where current and proposed protocols can be discussed in a multidisciplinary format.

Variation from standard practice outlined within a treatment protocol including individual drug dose variations may be clinically appropriate for individual patients, and reasons for such variation and discussion with the patient and/or carer should be clearly documented. Monitoring and analysis of protocol and dose variations at an institutional level should be possible with local agreement on methods and frequency of auditing such variations being in place.

Key annual scientific meetings (e.g. American Society of Clinical Oncology, San Antonio Breast Symposium and The American Society of Hematology) often report on study data that may have practice changing implications for protocols. It is useful to convene a protocol review meeting after conferences to consider any major changes required.

(Cancer Institute NSW)[9] ;(Carrington et al, 2010)[5] ;(National Chemotherapy Advisory Group, 2009)[10] ;(Goldspiel et al, 2015)[6]

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Table 2: Suggested content of the chemotherapy protocol

1 Protocol name and reference number (if applicable)

Care should be taken to distinguish protocols with similar names (e.g. CHOP/CHOP14, FOLFOX4/ FOLFOX6).[11]

2 Indication (e.g. tumour group and stage) and treatment intent

Multi-tumour protocols can lead to confusion over diagnosis and treatment intent and should not be used (e.g. weekly paclitaxel for lung/breast).

3 Other treatment modalities that may accompany the protocol

For example: Concurrent or sequential chemo radiation, surgery following neo-chemotherapy.

4 Special precautions and contraindications to treatment
  • Eligibility and exclusions.
  • Dose appropriate criteria to treat (e.g. based on relevant laboratory results and toxicities).[12]
  • Reasons for dose modification or exceptions that may occur (e.g. a notation that standard treatment dose is contraindicated if pre-existing comorbidity, organ dysfunction, or prior therapy exists).[12]
  • Dose limits for individual and cumulative doses per dose, cycle and lifetime.[6]
5 Pre-treatment investigations for first and subsequent cycles including suggested scheduling of investigations during treatment

For example: Blood tests, ECHO, tumour markers.

6 All medications that are part of the protocol including individual dosing parameters. Chemotherapy, targeted therapy and supportive therapy must be included.
  • All medications in the protocol must be listed using full generic names.[12]
  • Information should be present on the order of administration for each medication.
  • Abbreviations or acronyms to describe medication are potentially dangerous and should be avoided.[6]
  • Trial names for medication should not be used outside of a study protocol.
  • Care should be taken with naming where different formulations of a medication may exist (e.g. etoposide/etoposide phosphate, paclitaxel/NABpaclitaxel).
  • Tall Man Lettering should be applied to relevant medicines in electronic medication management systems, as outlined in the National Tall Man Lettering List.[13]
  • Doses must be written in the appropriate measurement/units and follow standards for abbreviations, trailing zeroes and leading zeroes.[12][14]
  • For doses calculated using Body Surface Area (BSA), Area Under the Curve (AUC) or Weight, a reference must be included to the methodology of the dose calculation or standard practice equations (e.g. calculation of creatinine clearance).[12]

For oral chemotherapy: [6]

  • Doses and schedules should be described as the amount of medication to be taken per dose, not as a total daily dose that is to be taken in divided doses.
  • The number of doses to be administered or taken should be clearly identified.
  • Instructions should address how medicines are to be taken with respect to food ingestion and indicate whether particular types of food may affect medication activity.
7 Route of administration of all medication
8 Scheduling

A dash mark should NEVER be used when communicating dosing schedules on specified days to avoid misinterpretation (e.g. day 1 AND 8 should be used, NOT days 1 – 8).[3][15]

9 Cycle frequency, the number of cycles and the total length of a treatment cycle or course

Protocol should specify the interval between repeated doses, the days on which each dose is to be given within a treatment cycle or course, and the total length of a treatment cycle or course.[6]

10 Medication vehicle and volume (where appropriate)

For example: Cyclophosphamide in sodium chloride 0.9%, 500 mL.

11 Rate and duration of administration
  • This should specify whether an infusion is intermittent or continuous.
  • Infusions that run over several days should clearly state the daily dose (i.e. amount to be administered during each 24 hour interval)[11] and total dose (e.g. 100 mg/m2 per day for days 1-7, total dose 700 mg/m2 over 7 days).
12 Adverse effects/regimen-specific complications that may occur during infusion/administration
  • For example: Hypersensitivity reactions, allergic reactions, cardiotoxicity, laryngo-pharyngeal dysaesthesia associated with oxaliplatin.
  • Specific recommended observation during an infusion should be stated.
13 Supportive therapy and concurrent medication
  • To include doses and scheduling (e.g. pre-medication, hypersensitivity medicines, hydration, anti emetics, haematopoietic growth factors, mesna etc).
  • Supportive therapies included where possible should be derived from evidence guidelines e.g. ASCO, National Comprehensive Cancer Network, Multinational Association of Supportive Care in Cancer (MASCC).[4]
14 Laboratory tests/investigations required to monitor toxicities and side effects

Parameters for initiating the next cycle of chemotherapy should be defined (e.g. neutrophil count > 1 x 109 /L for cycle to proceed).

15 Dose modifications for each agent in the protocol

This should be stated according to laboratory results (including blood and organ function tests) and side effects of treatment.

16 Potential interactions and medicines/agents/foods to be avoided
17 Expected side effects/toxicities, likelihood of onset and their management
18 Reference sources that support the use of the protocol in clinical practice and an assessment of the strength of evidence
  • If protocols vary from a standard, documented chemotherapy protocol then a supporting reference should be provided.
  • Where the protocol details vary from the detail in the original reference then the reasons should be stated clearly on the protocol (e.g. “This institute uses dose A and not dose B as stated in the original reference due to excessive toxicity reported with the original regimen”).
  • Ideally any changes should not be modified by hand but electronically changed or re-prescribed on the electronic prescribing system. If modified by hand there will be no auditable trail and there is the risk of subsequent cycles not including the change.

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  1. 1.0 1.1 Rozich JD, Howard RJ, Justeson JM, Macken PD, Lindsay ME, Resar RK. Standardization as a mechanism to improve safety in health care. Jt Comm J Qual Saf 2004 Jan;30(1):5-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14738031.
  2. 2.0 2.1 Womer RB, Tracy E, Soo-Hoo W, Bickert B, DiTaranto S, Barnsteiner JH. Multidisciplinary systems approach to chemotherapy safety: rebuilding processes and holding the gains. J Clin Oncol 2002 Dec 15;20(24):4705-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12488417.
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  5. 5.0 5.1 Carrington C, Stone L, Koczwara B, Searle C, Siderov J, Stevenson B, et al. The Clinical Oncological Society of Australia (COSA) guidelines for the safe prescribing, dispensing and administration of cancer chemotherapy. Asia Pac J Clin Oncol 2010 Sep;6(3):220-37 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20887505.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Goldspiel B, Hoffman JM, Griffith NL, Goodin S, DeChristoforo R, Montello CM, et al. ASHP guidelines on preventing medication errors with chemotherapy and biotherapy. Am J Health Syst Pharm 2015 Apr 15;72(8):e6-e35 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25825193.
  7. Dinning C, Branowicki P, O'Neill JB, Marino BL, Billett A. Chemotherapy error reduction: a multidisciplinary approach to create templated order sets. J Pediatr Oncol Nurs 2005 Jan;22(1):20-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15574723.
  8. Cohen MR. Hazard warning-vincristine overdose. Hosp Pharm, 1994;29:53.
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  10. National Chemotherapy Advisory Group. Chemotherapy Services in England: Ensuring quality and safety.; 2009 [cited 2016 Sep] Available from: http://webarchive.nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_104501.pdf.
  11. 11.0 11.1 Kohler DR, Montello MJ, Green L, Huntley C, High JL, Fallavollita A Jr, et al. Standardizing the expression and nomenclature of cancer treatment regimens. American Society of Health-System Pharmacist (ASHP), American Medical Association (AMA), American Nurses Association (ANA). Am J Health Syst Pharm 1998 Jan 15;55(2):137-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9465977.
  12. 12.0 12.1 12.2 12.3 12.4 Neuss MN, Gilmore TR, Belderson KM, Billett AL, Conti-Kalchik T, Harvet BE, et al. 2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology. Oncol Nurs Forum 2017 Jan 6;44(1):31-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28067033.
  13. Australian Commission on Safety and Quality in Health Care. National Standard for the Application of Tall Man Lettering: Project Report. Sydney: ACSQHC; 2011 Available from: https://www.safetyandquality.gov.au/wp-content/uploads/2013/03/National-Standard-for-the-Application-of-Tall-Man-Lettering-Project-Report-with-appendices-PDF-700KB.pdf.
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