A comparison of cancer treatment protocols in Australia, Canada, and the United Kingdom.

Introduction

The range of available cancer therapies has expanded rapidly in recent decades, yet differences remain in how these drugs are incorporated into national treatment protocols. Variation in drug selection and dosing across comparable healthcare systems may affect consistency of care and highlights the need for cross-country comparisons to support greater alignment in evidence-based practice [ 1 – 3 ].

Australia, Canada, and the United Kingdom (UK) are comparable high-income countries with universal or publicly funded (socialised) healthcare systems and established cancer care frameworks supported by national treatment guidelines [ 4 – 7 ]. Despite differences in healthcare structure, each system aims to deliver standardised oncology care [ 8 ]. Australia’s Pharmaceutical Benefits Scheme (PBS) operates under a hybrid public–private model and subsidises drugs based on cost-effectiveness [ 9 ]. Canada’s decentralised, province-led system results in regional variation in access [ 10 , 11 ], whereas the UK’s National Health Service (NHS) centralises decisions through nationally standardised protocols and assessments by the National Institute for Health and Care Excellence (NICE) [ 12 , 13 ].

Publicly available treatment protocols help guide chemotherapy prescribing within each country. These include eviQ in Australia, Cancer Care Ontario (CCO) in Canada, and the Systemic Anti-Cancer Therapy (SACT) protocols maintained by the Clatterbridge Cancer Centre (CCC) in the UK. Each provides structured, cancer-specific guidance on drug selection and dosing. However, differences in protocol content and categorisation can affect which drugs are recommended, how they are distributed across cancer types, and the consistency of dosing recommendations [ 14 – 16 ].

Although cross-country comparisons of cancer drug access and reimbursement have been widely explored [ 17 – 20 ], less attention has been given to the composition of chemotherapy drugs within national treatment protocols. In this paper, we compared the chemotherapy drugs included in the treatment protocols from Australia, Canada, and the UK. The analyses focused on variations in drug selection, their distribution across cancer types, and differences in dosing recommendations.

Materials and methods

Data collection

Data were collected between November 2024 and January 2025 from national cancer treatment protocols in Australia, Canada, and the UK. Chemotherapy drugs were identified by manually reviewing all treatment protocols from each country and selecting only those used to treat cancer. Drugs included solely for supportive care or the management of adverse effects were excluded.

Australian protocols were sourced from eviQ, a national database of evidence-based cancer treatment guidelines, excluding discontinued or superseded protocols. Canadian protocols were obtained from CCO, with drug funding status cross-checked using the Ontario Drug Formulary. For the UK, treatment protocols were taken from the SACT protocols published by the CCC NHS Foundation Trust, with funding information derived from guidance issued by NICE. Although detailed and widely used, the Clatterbridge protocols represent the practices of a single NHS trust and may not reflect protocols used at all UK sites. These repositories were selected as they are widely used, publicly accessible sources of structured chemotherapy guidance within each country, allowing cross-national comparison.

A master drug list was created for each country. For each drug, the following information was extracted: drug name, number of protocols in which it appeared, cancer types it was indicated for, funding status (whether subsidised for at least one indication), and dosage details. Where a drug appeared in multiple formulations (e.g. oral versus intravenous) with different dosages, each was treated as a separate entry. Drug names were standardised using generic names to ensure consistency across sources.

Data analysis

All analyses were performed using RStudio (version 2024.04.2 + 764) [ 21 ]. Descriptive comparisons were made to explore how drugs were used across different cancer types and countries. Summary statistics, including median, minimum, and maximum were calculated for dosing data. Cancer type terminology was standardised across the three countries, with haematologic cancers grouped under a single category. Differences in the distribution of drugs across cancer types between countries were assessed using a chi-square test of independence.

Dose analyses were conducted at the individual drug level across all protocols and stratified by cancer type to compare dosing practices across countries within the same cancer indication. Where cross-country dose comparisons were performed, values were converted to a consistent unit (mg/m²) assuming a body surface area of 1.73 m².

Visualisations were generated using the tidyverse package (version 2.0.0) [ 22 ]. A summary table of extracted drug data and calculated dose statistics is provided in the Supplementary Information.

Results

Summary statistics for Australia, Canada, and the UK are presented in Table 1 . Canada had the highest number of treatment protocols ( n = 1,171) and also the highest number of unique chemotherapy drugs ( n = 222), followed by Australia ( n = 168), and the UK ( n = 164). Funding coverage was high and similar across countries, with 84 to 89% of drugs subsidised for at least one cancer indication.

Figure 1 shows the overlap of chemotherapy drugs used in national protocols. Across the 2,450 protocols of all three countries, 243 unique drugs were identified. Of these, 123 (51%) were used in all three countries, and 175 (72%) were shared by at least two, indicating substantial overlap alongside country-specific differences. Canada and Australia shared 29 additional drugs not used in the UK, and Canada and the UK shared 22 not used in Australian protocols. Only one drug (tepotinib) was used in both Australia and the UK but not Canada. Several drugs were unique to a single country: 42 in Canada, 14 in the UK, and 12 in Australia. Many of these were newer targeted therapies, including kinase inhibitors and monoclonal antibodies. For example, Canada utilised fruquintinib, erdafitinib, and capmatinib; the UK listed tivozanib, nintendanib, and momelotinib; and Australia included ofatumumab, ivosidenib, and elotuzumab. Other country-specific entries reflected particular formulations or drug combinations, such as liposomal daunorubicin/cytarabine and pegylated liposomal doxorubicin (Canada), or micronised abiraterone (Australia).

Table 2 summarises the distribution of drugs across cancer types by country. Haematological malignancies accounted for the largest number of drugs in all three countries, with variation observed across other cancer groups. Differences in the distribution of drugs across cancer types were assessed using a chi-square test with Monte Carlo simulation (10,000 replicates).

We were unable to reject the null of independence implying that the frequencies of drugs by cancer type are not significantly different across countries (χ² = 17.61, p = 0.49).

Differences in recommended dosing were also identified for the same drug within comparable clinical indications across countries. However, some apparent differences are attributable to variation in administration schedules. For example, in the adjuvant treatment of non-seminomatous testicular cancer using the BEP regimen (bleomycin, etoposide, and cisplatin), apparent variation in cisplatin dosing reflected differences in administration schedules rather than total dose. The Australian eviQ protocols specified cisplatin 20 mg/m² IV on days 1 to 5 in a 21-day cycle, whereas the Canadian and UK protocols included an alternative schedule of 50 mg/m² IV on days 1 to 2 [ 23 – 28 ]. Despite this, the cumulative dose per cycle was equivalent (100 mg/m²), indicating that differences arose from scheduling rather than overall dose intensity.

Figure 2 shows the number of individual chemotherapy drugs used for each cancer type, grouped by country. Haematological malignancies had the highest number of unique drugs ( n = 129), with Canada contributing the most agents ( n = 108), followed by the UK ( n = 73) and Australia ( n = 69). The high number of unique drugs within haematological malignancies was influenced in part by acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), the two primary forms of paediatric leukaemia. These conditions are treated using multiple combination regimens delivered across distinct phases of therapy, including induction and consolidation, and, for the treatment of ALL, maintenance therapy. Different cytotoxic combinations are used at each stage, and additional protocol variants may exist within the same phase, resulting in a large number of distinct agents within a single disease category. Urogenital cancers ranked second, with Canada again contributing the most distinct drugs ( n = 62; 47%), compared with Australia [ 42 ], and the UK [ 28 ]. For respiratory cancers, Canada used 55 individual drugs, the UK 39, and Australia 33.

Across countries, high-incidence cancers such as haematologic, urogenital, respiratory, gastrointestinal, and breast cancers consistently featured the highest number of distinct drugs. In comparison, low-incidence or more specialised cancers were associated with a narrower selection of drugs. While general patterns were similar, slight differences in drug counts highlight variations in how drugs are selected and distributed across treatment protocols.

The minimum, median, and maximum recommended doses for the ten most frequently used chemotherapy agents across Australia, Canada, and the UK are shown in Fig. 3 (overall) and Fig. 4 (stratified by indication). These agents were selected based on the number of protocols in which each drug appeared across all three countries.

Vincristine dosing was similar in Australia (median 1.4 mg/m²; maximum 2 mg/m²) and the UK (median 1.45 mg/m²; maximum 2 mg/m²), whereas Canada reported higher median (2.4 mg/m²) and maximum (3.46 mg/m²) doses (Fig. 3 ). When analysed by indication, the doses are very similar, and the overall difference is being driven by the fact that only Canada has vincristine protocols for breast, gastrointestinal and urogenital cancers (Fig. 4 ). Doxorubicin showed comparable dose ranges in Australia and the UK (approximately 10–60 mg/m²), while Canada reported a wider range (17.3–130 mg/m²), with the highest median dose (86 mg/m²), Fig. 3 . When analysed by indication, Canada’s protocols specified higher maximum doses of doxorubicin across all indications studied (Fig. 4 ). Cisplatin dosing was broadly similar across countries. The UK had the lowest minimum dose (20 mg/m²), when used in a chemoradiation regimen for locally advanced NSCLC. In Australia, lower minimum doses (25 mg/m²) were used for advanced biliary and gallbladder cancers in combination regimens, and as fractionated dosing in head and neck cancer. Canada reported the highest median dose (82 mg/m²), followed by Australia (75 mg/m²). The UK had the lowest median (45 mg/m²) and maximum dose (80 mg/m²), with the latter close to Canada’s median.

Etoposide and paclitaxel showed wider dose ranges in Australian protocols (etoposide: 40–200 mg/m²; paclitaxel: 45–200 mg/m²), Fig. 3 . In comparison, UK protocols reported narrower ranges for paclitaxel (175–175 mg/m²), and Canada reported a median of 303 mg/m² and maximum of 345 mg/m², Fig. 3 . Cyclophosphamide median doses were similar across countries (600–625 mg/m²). Dexamethasone doses varied between countries. Australia reported a range of 8–40 mg/m² (median 20 mg/m²), while the UK reported 15 mg/m² and Canada reported 40 mg/m² (Fig. 3 ), however this was largely driven by the differencing indications dexamethasone was used for across the countries (Fig. 4 ).

Among monoclonal antibodies, apparent dosing differences primarily reflected alternative administration schedules rather than differences in cumulative dose (Fig. 5 ). For example, Canadian cetuximab protocols offered both 250 mg/m² weekly and 500 mg/m² every two weeks, while obinutuzumab in UK protocols for chronic lymphocytic leukaemia was split across the first two consecutive days of the cycle (100 mg and 900 mg), a strategy also seen in Australian and Canadian protocols. Similarly, atezolizumab protocols in Canada and the UK provided multiple dosing options (e.g., 840, 1200, and 1680 mg), whereas Australian protocols typically included only 1200 to 1680 mg. These differences reflect variations in administration schedules rather than differences in overall drug exposure per cycle.

Across the top 10 monoclonal antibodies, four showed variation in median doses between countries. In contrast, nine of the top 10 overall drugs, predominantly cytotoxics, showed variation in median doses. The coefficient of variation (CV) for median doses was 38.1% for cytotoxic agents and just 7.0% for monoclonal antibodies.

Discussion

This study compared national chemotherapy protocols across Australia, Canada, and the UK to assess alignment in drug selection and dosing practices. While 51% of chemotherapy drugs were shared across all three countries, 72% were used in at least two, indicating both overlap and divergence in protocol content. Country-specific drugs remained common, demonstrating that protocol composition is not fully aligned across these settings. Differences in drug incorporation were observed despite their comparable healthcare systems and access to similar bodies of clinical evidence [ 1 , 3 , 29 – 31 ]. Differences in drug approval and reimbursement timing were also observed. For example, larotrectinib was incorporated into Canadian protocols earlier than in Australia, where PBS listing occurred in 2022 for select NTRK-positive cancers, with broader indications added in late 2024, reflecting staggered alignment in access across countries [ 32 , 33 ].

The distribution of drugs across cancer types differed between countries. Protocols for common cancers like breast, gastrointestinal, respiratory, urogenital, and haematologic malignancies had the highest number of unique agents in all three countries. This is consistent with global patterns in cancer care, where drug development and funding tend to focus on cancers with higher incidence and burden [ 34 – 36 ]. In contrast, fewer drugs were listed for rare or low-incidence cancers, particularly in Australian protocols. The limited number of agents for these conditions reflects ongoing challenges in prioritising rare cancers, which often lack commercial incentives for drug development and therefore face slower regulatory and funding approvals [ 18 , 37 – 40 ]. CCO had the highest number of treatment protocols, which may reflect the decentralised structure of cancer care across provinces and the development of province-specific guidance. As observed in all three countries, haematological malignancies contributed substantially to the total number of protocols, consistent with the high degree of regimen complexity and the multi-phase structure of treatment in this disease group.

Aside from drug selection, we observed differences in the dosing practices for several commonly used chemotherapy agents. While most drugs showed broadly comparable dosing ranges across countries, vincristine, doxorubicin, and paclitaxel demonstrated considerable inter-country variation in minimum, median, or maximum recommended doses. For several drugs, Australia showed the widest range between minimum and maximum recommended doses, while Canada often reported higher median doses. Some of the observed differences in dose ranges likely reflect differences in national guideline development, funding mechanisms, and degree of protocol standardisation across countries. Canadian protocols frequently align with U.S.-based clinical trials and National Comprehensive Cancer Network (NCCN) guidance, which may favour higher dose intensity or alternative scheduling approaches when compared with European or Australasian frameworks. In curative settings or haematological malignancies, these protocols often support more intensive regimens (e.g. vincristine in paediatric or lymphoma protocols), which may contribute to the higher median and maximum doses observed in several Canadian regimens. In contrast, UK protocols are shaped by centralised NHS frameworks and formal technology appraisal processes conducted by NICE [ 13 , 41 ]. The CCC SACT protocols therefore tend to adopt more standardised dosing structures, often including defined dose caps (e.g. 175 mg/m² for paclitaxel), which may reduce variability between protocols. In Australia, the PBS funds specific regimens based on cost-effectiveness, which may encourage the use of lower-dose protocols for economic reasons.

The lower variability observed for monoclonal antibodies (CV = 7%) compared with cytotoxic agents (CV = 38.1%) likely reflects differences in the dosing strategies of these drug classes in clinical practice. Traditional cytotoxic agents were developed using maximum tolerated dose approaches, with doses established through toxicity-driven escalation studies. They are commonly administered according to body surface area (mg/m²), which individualises dosing based on patient size and permits adjustment for toxicity, treatment intent, tumour type, and co-administered agents [ 42 – 45 ]. As a result, cytotoxic regimens often demonstrate broader minimum and maximum dose ranges across protocols.

In contrast, monoclonal antibodies are typically developed using pharmacokinetic and pharmacodynamic modelling to achieve defined target-mediated exposure levels [ 44 , 46 , 47 ]. Dosing is frequently fixed or weight-based at pre-specified levels and is generally consistent across tumour types and treatment settings. Because these agents are not titrated to maximum tolerated dose in the same way as cytotoxics, their recommended doses tend to remain stable across protocols, resulting in narrower dosing ranges. Similar distinctions in dose variability between cytotoxic and targeted biologic therapies have been described in comparative analyses of international oncology guidelines [ 48 ].

Limitations

This analysis drew data from a single publicly available treatment protocol repository for each country: eviQ (Australia), Cancer Care Ontario (Canada), and the SACT protocols from the Clatterbridge Cancer Centre (UK). While these platforms are widely used and regularly updated, they do not capture all treatment pathways available within national health systems [ 48 , 49 ]. In practice, oncologists rely on a broader range of resources, including institutional guidelines, multidisciplinary team input, and emerging clinical trial evidence, which influence drug selection and dosing beyond what is documented and available to the public [ 50 , 51 ]. Consequently, the protocols analysed may not fully reflect real-world prescribing practices, where variability in clinician preference, institutional processes, and patient-specific factors can influence treatment decisions and implementation. Additionally, comparisons based on per-cycle dosing may not fully account for differences in administration schedules or treatment intent (e.g., curative vs. palliative), particularly for multi-day regimens or drugs with multiple approved dosing schedules, which may contribute to apparent variability in reported doses.

UK protocols were sourced from the CCC, representing the practice of a single NHS trust rather than a formally mandated national standard. Although broadly aligned with national guidance, separate protocols are developed across other NHS sites, and funding decisions are not entirely uniform across the UK, with differences between England and Scotland that may influence drug availability.

Conclusions

Chemotherapy drug use in Australia, Canada, and the UK overlapped moderately, with only 51% of drugs common to all three countries. Despite this, the inclusion of versatile agents, particularly established cytotoxics, was consistent across recommended protocols for high-incidence cancers and multiple tumour types. In total, 72% of drugs were shared by at least two countries, indicating broad alignment in foundational treatment approaches. However, differences remained in how drugs were categorised and dosed, particularly for rarer cancers. As cancer care grows more complex, international comparisons may help benchmark treatment approaches and identify opportunities for greater harmonisation and improved access to emerging or less commercially incentivised therapies. For rare cancers, where evidence is limited and patient numbers are small, global collaboration on protocol development and data sharing could be critical to ensuring equitable and evidence-based care [ 39 , 50 , 52 , 53 ].

Acknowledgements

The authors have no acknowledgments to declare.

Authors’ contributions

All authors (NJW, JL, AP, and RC) designed the study. JL collected and analysed the data and wrote the main manuscript. All authors reviewed and approved the final version.

Funding

The authors received no specific funding for this work.

Data availability

The data analysed for this study are available from [ https://www.eviq.org.au/medical-oncology ], [ https://www.cancercareontario.ca/en/drugformulary/regimens ] , and [ https://www.clatterbridgecc.nhs.uk/professionals/clinical-guidance/sact-protocols-and-guidance ].

Declarations

Ethics approval and consent to participate

Approval by a Human Research Ethics Committee was not required for our analysis of publicly available data.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

Data Availability Statement

The data analysed for this study are available from [ https://www.eviq.org.au/medical-oncology ], [ https://www.cancercareontario.ca/en/drugformulary/regimens ] , and [ https://www.clatterbridgecc.nhs.uk/professionals/clinical-guidance/sact-protocols-and-guidance ].