Introduction

Cancer continues to be one of the leading causes of mortality worldwide, with approximately 9.7 million deaths related to neoplasms in 2022 according to data provided by the International Agency for Research on Cancer (IARC). The IARC estimated that, in that same year, approximately 20 million new cases of neoplasms were diagnosed (excluding nonmelanoma skin tumours) and that this number would increase in 2025 to 35.0 million [1].

Chemotherapy is a therapeutic strategy used to treat cancer. Currently, there is a wide arsenal of drugs with antineoplastic activity, and although therapies directed at specific cancer cell targets are becoming increasingly numerous, conventional chemotherapy continues to be the predominant method of treating cancer. These latter drugs are more nonspecific and generate a greater number of associated side effects because they act not only on tumour cells but also on healthy cells [2].

The toxicity of different antineoplastic agents (ANP) has a negative influence on the quality of life of patients, as well as on their morbidity and mortality. Adverse reactions in organs and tissues with high and rapid cell multiplication, such as hair follicles, bone marrow, and organs of the digestive tract and reproductive system, are well known. However, it is the nausea and vomiting induced by these medications that are the side effects that most concern patients with neoplasms [3,4]. Poor control of nausea and vomiting can lead to deterioration of the physical condition of patients, thus affecting their quality of life [5,6] and potentially leading to cycle delays or dose reductions in planned cancer treatment, which could affect treatment efficacy.

From a different perspective, the exposure of nurses, pharmacists, doctors, laboratory technicians, drug transport personnel, patients and their caregivers to ANP is a potential health hazard. In addition, these compounds are potential environmental pollutants if they are disposed of improperly, which makes them a matter of immense concern in terms of medical safety and even the environmental safety of patients with cancer [7]. Until a few years ago, drug treatment for cancer was carried out in specialized units within hospital facilities. However, today, technological advances and improvements in quality of care have made it possible for most chemotherapies to be administered on an outpatient basis [8].

Therefore, given the sociocultural impact of cancer diagnosis [9], the complexity of oncological disease and its treatments, and the high fear of patients regarding the side effects and dangers derived from their exposure to ANP [2], it is not surprising that information is sought on these ANP, even many times on Web 2.0.

Web 2.0 resources have led to a substantive change in the communication of knowledge, favouring its dissemination by allowing the expansion and permeability of knowledge at a very low cost. In addition, Web 2.0 has integrated into the current information society, and far from diminishing the information available to society, Web 2.0 has an increasing number of initiatives that have enhanced this information. It is not unreasonable to classify the Web as the main means of obtaining health information [10].

Many people claim to look for health information on the Web, even before consulting with professionals, and, in relation to searches about medicines on the internet, most of them are due to a specific cause, such as episodic drug treatments [11]. Similarly, a good number of searches by the general public are made on “sensitive” topics related to health, so knowing the number of visits by a population of interest can be useful for making important decisions regarding health (therapies, treatments, medications, etc.) [12].

Wikipedia is an example of a Web 2.0 resource; it is an encyclopaedia edited in collaboration by volunteers from all over the world, has been available on the internet since 2003, and is currently the seventh most visited site on the internet [13]. Likewise, the articles (pages) it contains usually appear first in the results of main search engines, making Wikipedia the most visible and most consulted Web 2.0 resource [14].

Currently, it is essential that patients, families and caregivers seeking information about chemotherapy have access to information not only on the efficacy of the treatment but also on the chemical risk of exposure to these dangerous drugs (medication-related problems (MRPs)) and how to reduce, as much as possible, this exposure [15]. Therefore, the general population must learn and practice exposure prevention to reduce their risk of exposure to the minimum level possible.

However, although health education is generally indicated as part of the rational use of drugs to ensure treatment quality and patient safety [16], there is little awareness of the need to reduce the risk of exposure to ANP in the general population. To our knowledge, there is no campaign to prevent the risk of exposure to ANP for the general population.

Therefore, it is essential, on the one hand, to provide health education on the risk of exposure to ANP and, on the other hand, to control the information available in this regard on Web 2.0, as it is the main source of consultation for the general population.

Consequently, the objective of this study was to analyse the trend in the usage of the main ANP in Spain, to determine the association of this trend with the number of visits to the pages on these ANP in the Spanish edition of Wikipedia and to verify the existence of information tending to decrease the associated risks of ANP exposure.

Materials and Methods

Results

ANP use

From the data provided by the hospitals of the public network of the SNS, it was possible to determine the use of ANP for the years 2016 to 2022. During that period, more than 100,000 units of the 9 ANP under study were used (see Table 1).

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Table 1. Use of antineoplastic agents by hospitals in the public network of the Spanish National Health System.

https://doi.org/10.1371/journal.pone.0320773.t001

The ANP most used was fluorouracil, with a mean use of 332 280.57 ±  25798.39 units, a median use of 348 834 units, a maximum use of 409,649 units in 2016 and a minimum use of 209,809 units in 2022. The ANP with the lowest average use was cyclophosphamide, with a mean use of 113,953 ±  4,646.86 units, a median use of 118,871 units, a maximum use of 128468 units in 2021 and a minimum use of 96159 units in 2016 (see Table 1).

The temporal evolution of ANP use, as determined via a regression model, revealed a significant increasing trend, except for the use of oxaliplatin and etoposide, as shown in Table 1.

Number of visits to ANP Wikipedia pages

Analysis of number of visits to ANP Wikipedia pages allowed us to determine the annual number of visits to these pages in the Spanish edition of Wikipedia (see Table 2).

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Table 2. Annual number of visits on pages related to antineoplastic agents in the Spanish edition of Wikipedia.

https://doi.org/10.1371/journal.pone.0320773.t002

The ANP page most visited was that for rituximab, with a mean of 60061.00 ±  9832.51 visits, a median of 55432 visits, a maximum of 95028 visits in 2016 and a minimum of 31780 visits in 2022. The least visited ANP page was that for azacitidine, with a mean of 3038.57 ±  352.68 visits, a median of 2602 visits; a maximum of 4577 visits in 2018, and a minimum of 1966 visits in 2022 (see Table 2).

The temporal evolution ANP page visits, as determined via a regression model, showed a significant decreasing trend except for visits to the azacitidine page, which showed a very moderately decreasing trend that was not significant (see Table 2).

Association between the use of ANP and the number of visits to ANP pages in the Spanish edition of Wikipedia

The analysis of the correlation between ANP use and the number of visits to each ANP page in Wikipedia showed a strong inverse relationship for paclitaxel (R =  -0.87 p =  0.010), rituximab (R =  -0.97 p <  0.001), carboplatin (R =  -0.95 p =  0.001) and doxorubicin (R =  -0.82 p =  0.026), this indicates that as searches on Wikipedia increase, the consumption of these drugs tends to decrease, as shown in Fig 1. For the remaining ANP, no significant correlation was found between their use and the number of visits to their pages: fluorouracil (R =  0.38 p =  0.405), azacitidine (R =  -0.39 p =  0.392), oxaliplatin (R =  0.26 p 0.569), etoposide (R =  -0.34 p =  0.456) and cyclophosphamide (R =  -0.70 p =  0.079).

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Fig 1. Relationship between the use of antineoplastic agents (plotted on the horizontal axis) and the number of visits to the pages for these agents in the Spanish edition of Wikipedia (plotted on the ordinate axis).

https://doi.org/10.1371/journal.pone.0320773.g001

Criteria related to MPI

Analysis of the fulfilment of criteria related to the reduction in ANP-related risk showed that only one of these variables, indication/use, was included on the pages of the 9 (100%) ANP studied. Another adverse/secondary effect was included on the pages for 8 (88.88%) of the ANP (only the page for fluorouracil did not mention another adverse/secondary effect). The remaining variables related to MPI were not mentioned on even 50% of the ANP pages. On the other hand, the ANP page that fulfilled the most criteria was that for rituximab, fulfilling 5 (50%) of the 10 criteria. The remaining ANP pages fulfilled only 3 (30%) or 2 (20%) criteria (see Table 3).

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Table 3. Fulfilment of criteria on including links to databases containing medical-pharmaceutical information related to the reduction in the risk of using antineoplastic agents.

https://doi.org/10.1371/journal.pone.0320773.t003

Criteria related to SMI

Analysis of the fulfilment of criteria related to risk/safety information showed that the number of ANP pages for which these criteria were met was notably low. Only partial fulfilment of two criteria was verified: that of effects on pregnancy, information for which was included on the pages for 4 (44.44%) ANP (fluorouracil, oxaliplatin, carboplatin and doxorubicin), and that of effects on fertility, information for which was included on the pages for only 2 (22.22%) ANP (oxaliplatin and cyclophosphamide). Of note, the page for oxaliplatin included only 2 (13.33%) of the 15 criteria studied (Table 4).

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Table 4. Fulfilment of criteria on including links to databases containing safety measure information related to reducing the risk of using the antineoplastic agents.

https://doi.org/10.1371/journal.pone.0320773.t004

Existence of a link to a database containing MFI or SMI

Of the 9 ANP studied, only the page for fluorouracil included external links to the 3 databases that comprehensively include both MFI and the SMI. On the other hand, the pages for two of the ANP studied, rituximab and etoposide, did not include links to any of these 3 databases (see Table 5).

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Table 5. Existence of a link to a database that contains medical-pharmaceutical information or safety measure information for antineoplastic agents in the Spanish edition of Wikipedia.

https://doi.org/10.1371/journal.pone.0320773.t005

Discussion

The veracity of information about cytostatics is vital to ensure effective and safe treatments, to empower patients and to comply with ethical and legal standards. The inaccuracy or falsity of this information can have severe consequences, affecting both the health of patients and their caregivers and the health professionals who care for them. Thus, this work aimed to determine the general population’s interest in the information concerning the most consumed ANP in Spain and to determine whether the existing information in the Spanish edition of Wikipedia could be useful for reducing the associated risks.

A growing use of ANP was found to be related to the increase in cancer incidence both in Spain and worldwide. In the year 2022, the use of ANP accounted for one-quarter of hospital pharmacy total expenditures [28].

Horn et al. highlighted that, despite the increasing incidence of cancer, oxaliplatin and etoposide use did not increase. Oxaliplatin, a first-line ANP for gastrointestinal tumours, is used in both neoadjuvant and adjuvant settings. However, the lack of an increase in oxaliplatin use cannot be explained by a decrease in the incidence of gastrointestinal cancers, because colorectal cancer is among the top three cancers in incidence and prevalence [29]. In contrast, the lack of an increase in etoposide use could be explained by a decrease in the incidence of one of its main indications, small cell lung cancer, which accounts for 15–20% of lung cancers, with a median survival of 10 months [30,31]. Although immunotherapy has been incorporated as a therapeutic option in patients with these cancers, it is done so as a combined treatment; that is, the standard chemotherapy is administered along with a monoclonal antibody [32]. The decrease in etoposide use may also be due to the evidence for long-lasting clinical responses when this ANP is used at low and stable doses [33].

In contrast to the increase in ANP use, the population of interest showed a decreasing trend in searches on these ANP. In line with these data, the study by Eheman et al. [34] revealed that only 1 in 5 cancer patients reported actively searching for information at the time of treatment, and Shea-Budgell et al. [35] concluded that although the internet was a source of information used by these patients, they preferred communication with their doctor or health professional because they considered them to be a more reliable source. In another study, cancer patients frequently searched the Web for health information after their doctor’s appointment, perhaps because older people prefer direct consultation rather than using the internet to obtain health information [36]. In the study by Costas-Muniz et al. [37], only 2 out of 10 patients wanted additional information about their diagnosis or treatment.

One possible explanation is that although these drugs are more commonly used, they are often used in combination with other therapies (surgery, radiotherapy and chemotherapy), which makes it difficult for patients to fully understand the treatment they receive [38]. Epstein et al. [39] found that only 1 in 20 cancer patients who had survived for less than six months had an accurate understanding of their disease. In addition, chemotherapy causes important side effects (fatigue, nausea, vomiting, temporary hair loss, anaemia, infections, fertility problems, etc.), and these symptoms concern the patient and his or her environment and are the catalysts for most information searches [40,41].

The relationship between ANP use and searches for information on these ANP in the population interest showed in an inverse association. This trend has already been observed in other areas of study, especially when the symptoms or possible adverse effects are better known than the disease or the treatment [42]. This search for information is marked by the priority of responding to a need rather than informational interest. Law et al. [43] demonstrated this circumstance and concluded that the most frequent visits to medication pages were due to a specific cause, such as the possible consequences and MRPs of episodic pharmacological treatments. Thus, the work of Martínez-Aguilar et al. [44] showed that the population’s interest in MRPs was more inclined towards issues better known by the general population, such as overdose or contraindications.

Information on drugs is one of the most important aspects related to their use since having adequate information allows patients to obtain the best pharmacological treatment possible [45]. The misuse of medications by the patient is often due to their ignorance, which is generally due to a lack of information or understanding, misinterpretation or forgetfulness of the instructions that they received. Therefore, when a patient finds themselves alone and does not know how to use a medication on their own, on many occasions, they often end up consulting Wikipedia.

In this sense, the MFI included in the Spanish Wikipedia pages of the ANP studied was poor. There was an absence of information of real importance for those who consulted these pages. For example, no page presented information on what to do in case of RF, or no information was given on possible drug interactions [46].

Previous research on active medicinal ingredients, carried out in English, confirmed that important data, such as dosage, adverse effects and contraindications, are often lacking, resulting in serious damage to the health of patients [11]. Another study of 20 high-prescription drugs reported that the information on dosage and side effects was incomplete and inaccurate [47].

This situation is concerning given that U.S. doctors claim to use Wikipedia as one of their sources of information, and pharmacists themselves admit using Wikipedia in professional practice, recognizing that they are using Wikipedia increasingly more, even for educational purposes. For all of these health professionals, Wikipedia is the most commonly used Web resource, with the exception of Google [11].

There was no relationship of information presented on the Wikipedia page and the information in the Technical Data Sheets of the ANP studied. Technical Data Sheets include information on the need for dose adjustments in RF and HF, interactions, contraindications, effects on the ability to drive and use machines or waste management. This information is essential for the safe use of these ANP. The only information that all the pages included was the drug indication and its adverse effects.

Similarly, scarce data were provided in relation to SMI. This situation is very concerning given that therapeutic doses of ANP can clearly lead to harmful effects on patient health. Additionally, the possible adverse effects caused by chronic occupational exposure to low concentrations of these compounds are known, taking into account that these effects may be subclinical and may not be evident for years (or generations) after exposure. However, even in the absence of epidemiological data, the toxicity of ANP necessitates precautions to systematically minimize exposure [48]. For this reason, the lack of information on the risks of ANP use/manipulation, especially the lack of information on minimizing these risks, is remarkable.

In this study, no information on the risk of exposure to these ANP during breastfeeding was available; only 2 pages included information on the effects of the ANP on fertility, and 4 pages included information on the effects of the ANP on pregnancy.

Although it is known that there is no information on exposure to ANP in these populations because their use is contraindicated, there is also a lack of knowledge/misinformation on the potential risks of exposure in both healthcare professionals/staff and in caregivers and pregnant or breastfeeding family members. To date, these potential risks of exposure have not been studied, so a conservative attitude should be adopted, educating and warning of the dangers of exposure to these substances.

Furthermore, there was no information on safe use or occupational health, such as first aid, measures in case of accidental spillage, precautions in handling and storage, or exposure controls and individual protection. Moreover, no information on waste management or environmental pollution was provided. Additionally, there was a lack of information on the safe use of ANP at home, where measures should be taken in cleaning, laundry and excreta handling. Even less information was available on precautions in the use of ANP in veterinary medicine.

The National Institute for Occupational Safety and Health (NIOSH), in collaboration with several university programs, carried out an intervention to improve the content of occupational safety and health in Wikipedia [49]. This collaboration led the European Agency for Safety and Health at Work (EU-OSHA) to develop a “wiki” tool, OSHwiki [50], which would allow the sharing of knowledge about safety and health at work. However, a query did not return information on ANP in general or on those studied in particular, although it did return an entry on “dangerous substances”.

Along with concerns about the lack of both MFI and SMI, concern about the reliability of Wikipedia as a source of information in general is “advised”, although not very prominently, by the encyclopaedia itself, since in its entry “Wikipedia: Wikipedia is not a reliable source”, it is stated verbatim “Wikipedia is not a reliable source. Wikipedia can be edited by anyone at any time. This means that any information contained at any given time could be vandalism, a work in progress, or simply wrong” [51]. Furthermore, in another extensive entry on “Wikipedia reliability” there is a specific section on “Science and Medicine” where it is stated “Science and medicine are areas in which precision is of great importance and peer review is the rule. Although some Wikipedia content has undergone a form of peer review, most has not” [52]. The following page refers to a good number of academic works for and against the reliability of Wikipedia.

However, many people are unaware of these notices and may think that they receive adequate information. However, the spread of misleading MFI can cause significant harm to society and individuals, and, according to Hill et al. [53], it should be the responsibility of the content providers to solve this problem. Although Wikipedia is a free and collaboratively edited encyclopaedia, they must be responsible for the content that they disseminate, and it is no longer acceptable to hide behind the mantle of the “wiki”.

The criterion of a link to specialized databases that would provide detailed MFI and SMI can also be considered unfulfilled, especially in for the two ANP pages in which there was no link. A link to PubChem alone could provide sufficient information, even with its pictogram portrayal of chemical safety. However, it is important to note that PubChem information is presented in English (the study was conducted in the Spanish edition of the Wikipedia). Therefore, many people who consult the Spanish edition of Wikipedia may not understand English or have enough training to consult these databases properly.

Studies such as those of Leithner et al. [54] and Kupferberg et al. [55], recommended that commonly used, non-peer-reviewed websites that provide health information, such as Wikipedia, should include links to reliable, high-quality, and well-maintained sources.

To achieve an adequate understanding of risk in the population, the development of timely, efficient and effective communication strategies, led by health personnel with sufficient background, that allows individuals to adequately use the means of communication at their disposal or integrate this information appropriately in teams made up of professionals from different specialties, is needed, particularly for those designated to take on these tasks [55].

Nevertheless, links to external web pages are critical to increasing the information provided to users with access to a variety of additional perspectives, data, and resources. These links help support and complement the information presented, increasing the credibility and authority of the content. Additionally, by offering users the opportunity to further explore a specific topic through external links, deeper learning and a fuller understanding are encouraged.

In summary, having verified the deficiencies in the existing information in the Spanish edition of Wikipedia, it is necessary to be very cautious when consulting the information on ANP in Wikipedia. This does not mean that users will not find accurate and valuable information on Wikipedia; the information will be most of the time. However, Wikipedia cannot guarantee the validity of the information found on their site [56].