Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(1): 8–14

Original Research

10.5455/NJPPP.2025.v15.i1.2

Adverse drug reaction profile of taxanes: A prospective observational study among patients in a tertiary care hospital

Reeza Azeez¹, Kizhakkan Aboobakker Haseena¹ , Shehna A. Khader² and Mangattuvalappil Balakrishnan Sujatha^1*

¹Department of Pharmacology, Government Medical College Thrissur, Thrissur, India

²Department of Radiotherapy, Government Medical College Thrissur, Thrissur, India

*Corresponding Author: M. B. Sujatha. Department of Pharmacology, Government Medical College Thrissur, Thrissur, India. Email: mbsuja [at] gmail.com

Submitted: 29/03/2023 Accepted: 27/12/2024 Published: 31/01/2025

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Abstract

Background: Taxanes are a relatively newer class of anticancer drugs that are being extensively used in the management of various gynecological malignancies, breast cancer, lung cancer, and head and neck cancers in India as well as across the world. Despite its widespread use, not many studies have been conducted to evaluate the various adverse drug reactions (ADR) encountered with Taxanes in actual practice.

Aim: To study the ADR profile of Taxanes and to compare the ADRs of Paclitaxel and Docetaxel.

Materials and Methods: A prospective observational study of the patients being treated with taxanes for breast, lung, head, and neck and gynecological malignancies in the Radiotherapy outpatient department. Details regarding the ADR were collected via a questionnaire filled by direct interviews with the patients.

Results: Neutropenia was the most frequent ADR observed with Taxanes (both Paclitaxel and Docetaxel) based therapy accounting for 57% of all ADRs. Glove and stocking peripheral neuropathy was observed the most with Paclitaxel-based chemotherapy (70%) while neutropenia was the most frequent ADR associated with Docetaxel-based therapy (57%).

Conclusion: Neutropenia was the most common ADR observed with taxanes altogether and also with Docetaxel-based chemotherapy while peripheral neuropathy was the most frequent with Paclitaxel-based regimen.

Keywords: Cancer, Taxanes, Paclitaxel, Docetaxel, ADRs.

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Introduction

Cancer is a major cause of mortality and morbidity worldwide with the disease burden being projected to grow exponentially in the near future (Menon et al., 2018). The introduction of chemotherapeutic agents for cancer treatment has been beneficial in prolonging the lives of patients, reducing sufferings, and also curing the disease to an extent in at least some of the cancers. The different groups of anticancer drugs vary in their structure and mechanism of action.

Taxanes are a comparatively recent class of antineoplastic agents with a novel mechanism of action. They preferentially bind to microtubules than to tubulin dimers and promote the microtubule assembly and polymerization (Huizing et al., 1995). Paclitaxel, Docetaxel, and Cabazitaxel are the three approved taxanes that are currently available of which paclitaxel and docetaxel are the taxanes commonly used in clinical practice. Nab paclitaxel, a protein-bound form of paclitaxel is also available.

Taxanes play an essential role in the therapy of patients with ovarian, breast, lung, gastrointestinal, genitourinary, prostate, head and neck cancers (Brunton et al., 2017). Promising results have been observed with the combination of taxanes with cytotoxic drugs such as platinum compounds, doxorubicin, and 5- Fluorouracil (5-FU²). But the disappointing fact is that like any other antineoplastic agent, pharmacological action-related adverse drug reactions (ADR) have been reported with taxanes as well. As per the literature, the major toxicity encountered with paclitaxel is reversible myelosuppression and glove and stocking neuropathy. Nausea, myalgia, arthralgia, chest pain, mucositis, and edema could be the other troublesome adverse effects (Tripathi, 2018)^. Due to its poor water solubility, it was difficult to prepare a formulation of paclitaxel for i.v aqueous solution. Therefore, it is usually prepared in a solvent consisting of 50% Cremophor EL and 50% dehydrated alcohol (Huizing et al., 1995)^. Acute anaphylactoid reactions may occur because of this cremophor solvent. Neutropenia was found to be the major toxicity associated with docetaxel which was more than that with paclitaxel while neuropathy was found to be less frequent. Arrhythmias, fall in BP and fluid retention were found to occur with repeated courses (Tripathi, 2018).

Although taxanes have been in therapeutic use for quite some time and have emerged as one of the mainstay agents in the management of the most common malignancies including breast, lung, head, neck, and gynecological cancers, not many studies about their ADR in real life practice have been reported.

The only studies available in this regard at the time of initiation of this study were those by Fitzmaurice et al. (2015), Manohar et al. (2016) and Song et al. (2017). This study was undertaken with the aim of studying the common ADRs encountered with taxanes and also to compare the ADRs of Paclitaxel and Docetaxel.

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Materials and Methods

Study design and participants

This was a prospective observational study conducted among 420 patients being newly treated with taxanes for breast, lung, head, and neck, and gynecological malignancies in the Radiotherapy outpatient department (OPD) of Government Medical College, Thrissur, Kerala. The exclusion criteria included patients less than 18 and more than 75 years of age and those diagnosed with malignancies other than the specified ones. The study data were collected over a span of 12 months starting from October 2018 to October 2019. The study was commenced after approval from the Institutional Ethics Committee.

Sample size calculation

Sample size=420

According to the formula

where p=most prevalent adverse effect of Taxanes in the parent study, p=18.6%

q=(100–p)=81.4

d=20% of p

Zα=z score when α error < 5%.

Study procedure

After approval from the Institutional Ethics Committee of Government Medical College, Thrissur, patients satisfying the inclusion criteria were enrolled in the study. Informed consent was obtained from all the patients in the sample. At the first visit, the patient’s biodata and the details of the taxane therapy to be instituted were entered in the proforma. The patients were followed up at their third and sixth visits and information regarding ADR were obtained by interviewing them and noting them down in the questionnaire. The data were simultaneously being entered into an Excel sheet.

Data analysis

Data were entered in Windows MS Excel sheets and analyzed using SPSS V.20 software. Qualitative data were expressed in percentage. Quantitative data were expressed as mean and standard deviation.

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Results

In this prospective observational study, 420 patients diagnosed with breast, lung, head, and neck, or gynecological malignancies and treated with Taxanes as either monotherapy or in combination with other drugs in the Radiotherapy OPD of Government Medical College, Thrissur, were enrolled. They were assessed for the occurrence of ADRs.

The mean age group of the patients was 41–60 years, 63.1 % belonged to this group. The mean age of the study population was 55 ± 9.7904 years. Among the 420 study subjects, 70% were females and 30% were males. Only 29% of the study population were associated with a positive family history. Diabetes was found to be the most common comorbidity observed in 77 patients closely followed by hypertension seen in 76 patients. Smoking was the most frequently observed risk factor which accounted for 21.9% followed by alcoholism in 14.2% and chewing in 3.3% of the patients.

Among the 4 types of cancers evaluated, gynecological malignancies were found to be the most frequent. 142 out of 420 (33.8%) had gynecological cancers followed by breast cancer in 131 (31.2%) patients, lung cancer in 111 patients (26.4%), and head and neck cancer in 36 patients (8.6%) (Fig. 1) Ovarian cancer accounted for 67% of the gynecological malignancies in the study population followed by endometrial cancer in 25.3% and cervical cancer in 7.7%, respectively.

Paclitaxel and Docetaxel were the 2 taxanes that were prescribed in our study population. Out of the 420 patients, 211 were treated with Paclitaxel-based chemotherapy, and the rest 209 patients received docetaxel-based chemotherapy both accounting for approximately 50% each (Fig. 2).

Fig. 1. Diagnosis of the patient.

Among the 211 patients who received paclitaxel-based therapy, paclitaxel plus carboplatin combination was the most frequent observed in 156 (74%) of the patients followed by 48 (23%) who received paclitaxel alone. Nabpaclitaxel alone, nabpaclitaxel plus carboplatin, and paclitaxel plus trastuzumab were administered in 2 patients each accounting for 1% each.

Out of the 209 patients who were treated with docetaxel-based therapy, 121 (58%) received docetaxel as monotherapy, 48 patients (23%) received docetaxel plus carboplatin, 24 (11%) were given docetaxel in combination with cisplatin, and 5-FU, 12 persons received docetaxel with trastuzumab and 4 received it with carboplatin and 5-FU.

During the analysis of the pattern of incidence of ADRs, alopecia was excluded as it was observed with almost all of the patients and was reversible. Out of the 420 patients followed up in the study, 45 were advised palliative therapy from a local hospital due to poor prognosis, 10 patients succumbed to death and 9 patients did not present with any adverse effect other than alopecia. Among the remaining 356 patients, neutropenia was found to be the most common adverse effect considering both taxanes together which was observed in 203 out of 356.

Fig. 2. Paclitaxel versus Docetaxel based chemotherapy.

Fig. 3. ADRs observed with taxanes.

Among the patients treated with paclitaxel-based regimen, peripheral neuropathy was observed to be the most common adverse effect.

Neutropenia was found to be the most common adverse effect in patients managed with docetaxel-based regimen.

The majority of the reported ADRs were Type A reactions as per the Rawlins and Thomson ADR classification. Most of the ADRs were “Probable” (61.9%) whereas none of the ADRs were definitely due to Taxanes upon causality assessment by Naranjo’s algorithm. 93.3% of the ADRs were mild and only 6.7% were of moderate severity as per severity assessment by Modified Hartwig and Seigel +-scale. The preventability assessment of ADRs was carried out using Modified Schumock and Thornton scale and 93.6% were found to be not preventable while 6.4% were probably preventable (Tables 1-6).

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Discussion

The primary aim of this study was to study the ADR profile of taxanes and to make a comparison between Paclitaxel and Docetaxel. During the analysis of the ADRs, alopecia was excluded as it was observed in almost all the patients and was reversible and allergy was not observed in any of the patients probably because of the efficient premedications.

Considering the ADRs of both paclitaxel and docetaxel together, neutropenia was the most common (57%) followed by tastelessness (45.2%), myalgia (39.3%), peripheral neuropathy (37.9%), anemia (36.5%) and mucositis (31.2%) (Fig. 3). Peripheral (glove and stocking) neuropathy was the most frequent adverse effect observed in 70% of the patients treated with Paclitaxel-based therapy. Other significant adverse effects observed with paclitaxel were myalgia (67.5%), neutropenia (54.3%), tastelessness (43.6%), and anemia (31.4%). Constipation, arthralgia, mucositis, blackish discoloration of nails, chest pain, and diarrhoea were some of the other side effects that were seen in a relatively lower proportion of patients. Coming to Docetaxel-based therapy, neutropenia was the most common adverse effect accounting for 57.1% followed by tastelessness (44.6%), anemia (40.1%), and mucositis (36.7%). The incidence of ADRs were found to be slightly higher with paclitaxel-based therapy.

Table 1. Type of Paclitaxel based regimen.

Table 2. Type of Docetaxel based regimen.

Table 3. Distribution of ADRs with taxanes.

Table 4. Distribution of ADRs with Paclitaxel based therapy.

Table 5. Distribution of ADRs with Docetaxel based therapy.

The sample size of this study was 420 which was comparable to that of the study conducted by Fitzmaurice et al. (2015) in Tamil Nadu wherein 488 patients were enrolled (Manohar et al., 2016) while 1516 patients had participated in a similar study conducted by Song et al. (2017) in Korea (Song et al., 2017). In this study, the majority of the patients (63.1%) belonged to the age group of 41–60 years and the mean age of the study population was 55 ± 9.7904 years. In similar studies conducted by Fitzmaurice et al. (2015) and Manohar et al. (2016) there was a predominance of patients in the age group of 41–60 years (Manohar et al., 2016; Guduru et al., 2019). 70% of the patients in this study were females and only 30% were males. This could be probably because 2 major malignancies included in our study criteria were breast and gynecological malignancies accounting for the high female preponderance.

Table 6. Causality assessment of ADRs by Naranjo’s Algorithm.

Among the 4 types of malignancies included in the study criteria, gynecological malignancies were found to be most frequent in the study population accounting for 142 out of 420 patients (33.8%) followed by breast cancer in 131 patients (31.2%) then lung cancer in 111 (26.4%) and least common were head and neck cancers in 36 patients (8.6%). In the study by Manohar et al. (2016) in Karnataka, the trend was quite different wherein breast cancer was the most frequent malignancy accounting for 40% followed by gynaecological cancers (20%) then head and neck cancers (13.3%) and lung cancer was the least common (3.3%) (Guduru et al., 2019). In the current study, among gynecological malignancies ovarian cancer was the most common (67%) followed by endometrial cancer (25.3%) and then cervical cancer (7.7%). However, in the study conducted by Chhabra et al. (2002) in Maharashtra, cervical cancer accounted for 80% of the cases followed by ovarian cancer (15%) and endometrial cancer only in 2% (Chhabra et al., 2002).

In this study, both Paclitaxel and Docetaxel-based regimens were used equally (nearly 50% each). However, in the study conducted by Song et al. (2017) in Korea, Docetaxel-based therapy was administered in 77% whereas Paclitaxel-based regimen only in 23%^6. In this study, paclitaxel plus carboplatin combination was the most frequently used which was administered in 156 out of 211 patients (74%). This was similar to the findings of the study by Manohar et al. (2016) while in the study by Jire et al. (2016) the combination of paclitaxel, cisplatin, and 5-FU was commonly used (Guduru et al., 2019). Among the patients receiving docetaxel-based chemotherapy, docetaxel monotherapy that was used in 121 out of 209 patients (54%) was the most common.

As mentioned above, neutropenia was observed as the most frequent adverse effect considering the statistics of both taxanes together in this study. However, in a similar study by Fitzmaurice et al. (2015) the most commonly observed ADRs were anemia (18.6%), diarrhoea (16.9%), candidiasis (11.9%), and peripheral neuropathy (6.8%) (Manohar et al., 2016). In the study conducted by Guduru et al. (2019) the incidence of ADRs in the descending order of occurrence were alopecia (67%), peripheral neuropathy (57%), taste change (53%), mucositis and edema (43%), constipation (23%), arthralgia and myalgia (20%), diarrhoea (13%), and chest pain (3.3%) (Guduru et al., 2019).

According to a study by Marupudi et al. (2007) the major toxicities associated with paclitaxel were hypersensitivity, myelosuppression, peripheral neuropathy, cardiac disturbances, and myalgia (Marupu et al., 2007) in contrast to the preponderance of peripheral neuropathy observed in our study. In a study by Ho and Mackey (2014), the major adverse effects associated with docetaxel were acute infusion reactions, myelosuppression, fluid retention, cutaneous toxicity, and pneumonitis (Ho and Mackey 2014) whereas neutropenia, tastelessness, anemia, and mucositis were mainly observed with docetaxel in our study.

Upon assessment by Naranjo’s algorithm, 61.9% ADRs were found to be “probable” and 38.1% were graded as “possible”. The grade of causality of each ADR remained low due to the presence of co-administered drugs. In the study by Fitzmaurice et al. (2015)using Naranjo’s algorithm 49.5% of the ADRs were found to be “probable” and 50.5% were found as “possible” (Manohar et al., 2016).

Using the modified Hartwig and Seigel ADR severity assessment scale, 93.3% of the ADRs were mild and 6.7% of the ADRs were categorized as moderate in this study. There were no severe reactions reported. In the study by Fitzmaurice et al. (2015) most of the reactions were of mild level 1 severity while some cases of candidiasis and febrile neutropenia were of moderate level 3 severity (Manohar et al., 2016).

In the current study, 93.6% of the ADRs were not preventable and only 6.4% were probably preventable upon assessment by modified Schumock and Thornton scale. In a similar study by Fitzmaurice et al. (2015) 51.5% were probably preventable, 27.8% were not preventable, while 20.6% were definitely preventable (Manohar et al., 2016).

All the observed ADRs were managed symptomatically. Effective premedications helped to reduce the hypersensitivity reactions and vomiting associated with taxanes to a large extent. For severe neutropenia, patients were managed with granulocyte colony-stimulating factors. If the patients presented with chest complaints, the infusion of the anticancer drug was temporarily stopped and then restarted once the patient was stable.

Limitations of the study

As it was an observational study, dechallenge of the drugs were not possible and rechallenge is not ethically feasible. The study was confined to a small population in the Radiotherapy department of a Tertiary Care Hospital which may not represent the general population. Since the information regarding the ADRs were obtained via the questionnaire method there are chances of under-reporting and incomplete documentation of data. Some adverse reactions can appear late in the course of the therapy. As the taxanes were administered as combination therapy with other drugs in many patients, the causality assessment was difficult. Therefore, the overall occurrence of ADRs throughout the anti-cancer therapy could not be estimated.

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Conclusion

From the findings of this study, it was inferred that neutropenia was the most common ADR observed with both the taxanes together (57%). Peripheral neuropathy was the most frequent ADR observed with paclitaxel-based regimen (70%). Again neutropenia was the most common ADR with docetaxel-based therapy (57.1%). The incidence of ADRs was slightly higher with paclitaxel-based therapy than docetaxel-based therapy.

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Acknowledgment

We thank the participants of this study and the Department of Radiotherapy, Government Medical College Thrissur for their invaluable contribution.

Conflicts of interest

There are no conflicts of interest.

Funding

This work was conducted without funding from any funding body.

Authors contributions

Development of the research idea, selection of the research method, data collection and curation, formal analysis of the data, and writing of the first draft of manuscript was done by the main author. The co-authors had helped with the selection of the research topic, reviewed and provided the necessary amendments to the original manuscript, and also provided an overall guidance and supervision for the study.

Data availability

As the study was conducted in a tertiary care hospital within the region, a sufficient number of patients were available for inclusion in the research. But at the same time as we are dealing with cancer, a disease with high mortality and morbidity follow up of a few samples was not possible. Out of the 420 patients followed up in the study, 45 were advised palliative therapy from the local hospital due to poor prognosis, 10 patients succumbed to death and 9 patients did not present with any adverse effects other than alopecia. Therefore, altogether 64 patients were not included in the assessment of adverse drug reaction, leaving behind 356 patients only to be followed up for ADR.

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List of Abbreviations

Adverse drug reaction (ADR)

5- Fluorouracil (5-FU)

Outpatient Department (OPD)

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References

Brunton, L., Knollman, B. and Hilal-Dandan, R. 2017. Goodman and Gilman- The Pharmacological Basis of Therapeutics, 13th edition. New York City, NY: McGraw Hill Professional.

Chhabra, S., Sonak, M., Prem, V. and Sharma, S. 2002. Gynaecological malignancies in a rural institute in India. J. Obstetr. Gynaecol. 22(4), 426–429.

Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Dicker, D., Pain, A., Hamavid, H., Moradi-Lakeh, M. and MacIntyre, M.F., Allen, C., Hansen, G., Woodbrook, R., Wolfe, C., Hamadeh, R.R., Moore, A., Werdecker, A., Gessner, B.D., Te Ao, B., McMahon, B., Karimkhani, C., Yu, C., Cooke, G.S., Schwebel, D.C., Carpenter, D.O., Pereira, D.M., Nash, D., .Kazi, D.S., De Leo, D., Plass, D., Ukwaja, K.N., Thurston, G.D., Yun Jin, K., Simard, E.P., Mills, E., Park, E.K., Catalá-López, F., deVeber, G., Gotay, C., Khan, G., Hosgood, H.D. 3rd., Santos, I.S., Leasher, J.L., Singh, J., Leigh, J., Jonas, J.B., Sanabria, J., Beardsley, J., Jacobsen, K.H., Takahashi, K., Franklin, R.C., Ronfani, L., Montico, M., Naldi, L., Tonelli, M., Geleijnse, J., Petzold, M., Shrime, M.G., Younis, M., Yonemoto, N., Breitborde, N., Yip, P., Pourmalek, F., Lotufo, P.A., Esteghamati, A., Hankey, G.J., Ali, R., Lunevicius, R., Malekzadeh, R., Dellavalle, R., Weintraub, R., Lucas, R., Hay, R., Rojas-Rueda, D., Westerman, R., Sepanlou, S.G., Nolte, S., Patten, S., Weichenthal, S., Abera, S.F., Fereshtehnejad, S.M., Shiue, I., Driscoll, T., Vasankari, T., Alsharif, U., Rahimi-Movaghar, V., Vlassov, V.V., Marcenes, W.S., Mekonnen, W., Melaku, Y.A., Yano, Y., Artaman, A., Campos, I., MacLachlan, J., Mueller, U., Kim, D., Trillini, M., Eshrati, B., Williams, H.C., Shibuya, K., Dandona, R., Murthy, K., Cowie, B., Amare, A.T., Antonio, C.A., Castañeda-Orjuela, C., van Gool, C.H., Violante, F., Oh, I.H., Deribe, K., Soreide, K., Knibbs, L., Kereselidze, M., Green, M., Cardenas, R., Roy, N., Tillmann, T., Li, Y., Krueger, H., Monasta, L., Dey, S., Sheikhbahaei, S., Hafezi-Nejad, N., Kumar, G.A., Sreeramareddy, C.T., Dandona, L., Wang, H., Vollset, S.E., Mokdad, A., Salomon, J.A., Lozano, R., Vos, T., Forouzanfar, M., Lopez, A., Murray, C. and Naghavi, M. 2015. The Global Burden of Cancer 2013. JAMA Oncol. 1(4), 505–527.

Guduru, H., Jeevanagi, S.K., Nigudgi, S. and Bhandare, S.V. 2019. A prospective study on the prescription pattern of anti-cancer drugs and adverse drug reaction in a tertiary care hospital. IJBCP. 8(2), 200–205.

Ho, M.Y. and Mackey, J.R. 2014. Presentation and management of docetaxel-related adverse effects in patients with breast cancer. Cancer Manag. Res. 6, 253–259.

Huizing, M.T., Misser, V.H., Pieters, R.C., Ten Bokkel Huinink, W.W., Veenhof, C.H., Vermorken, J.B., Pinedo, H.M. and Beijnen, J.H. 1995. Taxanes: a new class of antitumor agents. Cancer Investig. J. 13(4), 381–404.

Jire, A.S., Bajait, C.S., Mahobia, V.K. and Motghare, V.M. 2016. Study of prescription pattern and adverse drug reactions in patients with cervical cancer in tertiary care teaching institute. Int. J. Basic. Clin. Pharmacol. 5(4), 1594–1597.

Manohar, H.D., Adiga, S., Thomas, J. and Sharma, A. 2016. ADR profile of microtubule damaging antineoplastic drugs. IJP. 48(5), 509–514.

Menon, A., Handattu, S., Shetty, J. and Girisha, B.S. 2018. Study of cutaneous advere effects of cancer chemotherapy. Clin. Dermatol. Rev. 2, 19–24.

Marupudi, N.I. Han, J.E., Li, K.W., Renard, V.M., Tyler, B.M. and Brem, H. 2007. Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin. Drug Saf. 6(5), 609–621.

Song SJ, Min J, Suh SY, Jung SH, Hahn HJ, Im SA, Lee JY. 2017. Incidence of taxane-induced peripheral neuropathy receiving treatment and prescription patterns in patients with breast cancer. Support Care Cancer 25(7), 2241–2248.

Tripathi, K.D. 2018. Essentials of Medical Pharmacology, 8th edition. Chennai, India: Jaypee Brothers medical publishers.