For citation purposes: Thakur A, Thakur JS. Extravasational toxicity of anticancer chemotherapy and its management. OA Case Reports 2013 Mar 01;2(3):26.



Extravasational toxicity of anticancer chemotherapy and its management

A Thakur1, JS Thakur2*

Authors affiliations

(1) Department of Pharmacology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, 171001, India

(2) Department of Otolaryngology-Head and Neck Surgery, Indira Gandhi Medical College, Shimla, Himachal Pradesh, 171001, India

* Corresponding author Email:



Anticancer drugs have a number of side effects, including toxic effects on bone marrow, kidney, lymphoreticular tissue, mucosa and cochlea. Extravasational toxicity is a complication of anticancer drugs, unmentioned in the majority of clinical textbooks other than oncology, explaining why residents may be unaware of this preventable catastrophe. The objective of this paper is to review and present the clinical features and management of extravasation of these anticancer drugs so that first line staff get acquainted to this complication and its management. After reading this paper, residents and clinicians will be more vigilant in anticancer drug infusion and management of extravasation.


Once extravasation occurs, tissue injury is inevitable but can be reduced with the proper antidote. A trained member of staff should administer this, preferably from the oncology department only.


As the incidence of cancer is increasing, cancer management has become a team effort consisting of family members, physicians, surgeons, radiations and medical oncologists, psychiatrists and physiotherapists. The objective of this team is to provide a cure or palliation with minimal side effects and quality of life to the patient.

Radiation therapy has become target-orientated to avoid injury to normal tissue but now chemoradiation is the preferred modality. In spite of giving promising results, these anticancer drugs have a number of side effects, which include toxic effects on bone marrow, kidney, lymphoreticular tissue, mucosa and cochlea[1]. In India, the oncology department is overloaded with cancer patients; hence, anticancer drugs are being infused in the parent departments by nurses and residents. However, extravasational toxicity is one of the dreaded complications of anticancer drugs, which did not find a place in the majority of clinical textbooks[1,2,3,4,5,6,7] other than oncology, and hence many of the residents may be unaware of this preventable catastrophe[8].

The incidence of extravasations in adults is 0.1% to 6.5%[9,10]. Extravasation can occur in any centre and even in highly advanced oncology centres[11], but these advanced centres have specially trained oncology-nursing staff. Commonly, chemotherapy is infused in clinical or parental departments of the patient, and work of infusion is left to a house surgeon or an intern, who may not have yet acquired a reasonable experience in venepuncture. Even the resident may not have adequate knowledge of the measures to be undertaken in case of extravasation due to absence of this complication and its management in the majority of clinical textbooks.

The objective of this paper is to review and present the clinical features and management of extravasation of these anticancer drugs so that the first line staff (residents/nurses) gets acquainted to this complication and its management.


The authors have referenced some of their own studies in this review. These referenced studies have been conducted in accordance with the Declaration of Helsinki (1964), and the protocols of these studies have been approved by the relevant ethics committees related to the institution in which they were performed. All human subjects, in these referenced studies, gave informed consent to participate in these studies.

Classification based on mode of tissue injury

Extravasation of anticancer drugs causes tissue damage by different mechanisms[12]: (a) DNA-binding drugs are initially absorbed locally causing direct cell death. Later, the drug is released from the nearby dead cells and causes further damage in surrounding tissue[10,13,14]. (b) Non-DNA-binding drugs are metabolized and cleared early; thus, tissue damage is less and easily neutralized by the antidote[12].

On the basis of extravasational toxicity, anticancer drugs are classified as irritants or vesicants (Table 1)[8,9,15,16].

Table 1

Vesicant and irritant chemotherapeutic drugs

Vesicant drugs: They cause blister formation, tissue death and ulcer formation at extravasation site.

Irritant drugs: They act as irritants on the injection site, and pain is the main symptom. Ulcer formation is rare but extravasation of large amount can lead to ulceration.

Guidelines for infusion of cytotoxic drugs

Institutional policy

There are specific guidelines for infusion of anticancer drugs[15,17,18,19,20,21],but the institutes or hospitals should also have their own policy on chemotherapy infusion. The attending physician and nursing staff should be familiar with the anticancer drug and its complication. The infusion should be given at the time of maximum staff strength and care. The ward should have information charts displayed both for staff and patient[22]. All the antidote drugs should be at the bedside of the patient. Patient should be informed about the symptoms of extravasation and its complications, and explained that despite best efforts, extravasation can occur[22]. All extravasation incidences should be brought to the notice of the department and institutional oncology board. They can review the case and decide on further management of the patient and preventive measures.

Intravenous access

This is the most important step in the prevention of extravasation. First of all, assess the general condition and age of the patient. Patient with paralysis, sensory deficit, tracheostomy or impaired higher mental function needs extra care due to inability to alert the staff during extravasation[23]. Elderly patients have increased risk of extravasation due to fragile veins. Similar risk is involved with deep veins, previous infusion within 48 h, multiple attempts for venous access, radiation or regional lymph node clearance of the limb[15,22].

The second most important step is to decide on central or peripheral intravenous access. Commonly, peripheral intravenous access is preferred. However, drugs to be given longer than 1 h should be administered only via a central line[15,23,24]. The flexible intracatheter devices should be used, as other rigid devices have a tendency for vessel injury[8,15]. Forearm is the preferred site due to catheter stability and muscle protection for the nerve and tendons in the event of extravasation, which is inevitable in case of access on hand or wrist[8].Venous access should be secured in a single attempt and in case of failure, the site should be changed to another proximal vein. The device should be covered with transparent dressing so that the signs of extravasation are visible to the patient and staff. Intravenous access should be checked by running normal saline intravenously. This step immediately confirms extravasation and also hydrates the patient, a prerequisite for chemotherapy. Now, anticancer drugs are started, and the patient is instructed to alert the attending staff if there is any pain, itching, stoppage of infusion or oedema in the limb.

Clinical features of extravasation

Extravasation of cytotoxic drugs leads to stoppage of infusion, and the patient will complain of excruciating pain and itching in the infusion site. Within a few hours, the extravasation area will show erythema, oedema and induration. Without intervention, these sign and symptoms will increase, and skin will show discolouration and desquamation of epidermis or blister formation in a few days. Extravasation of a large dose of cytotoxic drug leads to ischaemia and ulcer formation (Figure 1).

Extravasation on the forearm leading to skin necrosis.

Management of extravasation

• Immediate bedside management: Immediate management of extravasation reduces the tissue injury, and morbidity is inevitable if this step is delayed. On extravasation, infusion of drug should be stopped at once and normal saline infusion should be started. In case of an irritant drug, intravenous cannula should be removed while it is left in place in case of vesicant drug and proper antidote should be given[15]. The limb is elevated, and cold pack is applied to the local site. Hot packs are applied in extravasation of vinca alkaloids, as it causes vasodilatation and diffusion of the drug from the site. Parenteral strong analgesic helps in the reduction of inflammatory reaction and its symptoms.

• Use specific antidotes: There are a number of studies and case reports in literature[9,10,18,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45] to show the efficacy of various antidotes for extravasation of anticancer drugs.

a) Dimethylesulfoxide (DMSO): This drug is applied topically in case of extravasation of anthracyclines and mitomycin C. 1–2 ml of 1 mM 50%–99% DMSO is applied to the effective area thrice a day for 1–2 weeks. Oliver et al.[25] used topical DMSO every 6 h for 14 days in 20 patients with extravasation of anthracycline and in a follow-up of 16 patients for 3 months; no patient developed skin ulceration or necrosis. Bertelli et al.[27] used 99% DMSO topically every 8 h for 7 days in 127 patients with various vesicant drugs, and only one patient had skin ulceration.

b) Hyaluronidase: This drug breaks hyaluronic acid and increases the permeability of connective tissue and hence the diffusion of extravasated drug[10,15,24]. It is recommended in vinca alkaloids, epipodophylotoxin and taxanes[26,31] extravasations. It is injected through the existing cannula or subcutaneously in a clockwise manner if cannula has been removed. About 1–6 ml of 150 U/ml hyaluronidase is sufficient, but its dose corresponds to the amount of extravasated drug. It is contraindicated in case of infection and cancerous infiltration of the site, as it can ease the spread of disease.

c) Dexrazoxane: It is a recent FDA-approved antidote for anthracycline extravasation. Exact mechanism of action is unknown but some evidences suggest reversible topoisomerase II inhibition and binding to iron, which prevents the formation of free radicals responsible for tissue injury[22,32]. It is infused slowly over 1–2 h in a large vein other than the injured vein in a dose of 1 gm m[-2] within 6 h of extravasation, and repeated again on the second day with the same dose and 500 mg m[-2] on the third day. Based on anecdotal reports, DMSO interacts with dexrazoxane and decreases its efficacy; therefore, concurrent use should be avoided[32]. Fever, fatigue, gastrointestinal disturbances, headache, transient elevation of liver transaminases and decrease in blood count are a few of the side effects.

d) Sodium thiosulfate: This drug is indicated in extravasation of mustine HCl and cisplatin. Its exact mechanism of action is also unknown, but is thought to chemically neutralize the reactive alkylating species of mustine HCl and decrease the production of hydroxyl radicals[33].

e) Miscellaneous drugs: This group includes drugs with low level of evidence in the management of extravasation of anthracycline. These drugs have shown efficacy in experimental animals only, and include vitamin C[34,35], and E[36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59], heparin fraction[41], melatonin[42], hyperbaric oxygen[43]. Scuderi et al.[44] have reported local injection of saline (20–90 ml) with occlusive topical application of corticosteroid to avoid skin necrosis. Local infiltration of hydrocortisone in anthracycline extravasation did not prevent skin necrosis in mice model[45].

• Surgical intervention: Surgical intervention is reserved in cases that have not received antidote or presented late with erythema or necrosis. In two studies[46,47], saline washout with liposuction prevented skin necrosis, performed within 24 h of various extravasation injuries. This procedure is performed by irrigating the subcutaneous tissue with normal saline through a 4-mm blunt tipped liposuction cannula, and removing subcutaneous tissue with the extravasated drug.

Untreated extravasation leads to skin necrosis and needs plastic surgeon intervention. Surgical intervention involves two approaches[48,49,50,51,52,53,54,55].One approach involves extensive surgical debridement preferably under fluorescence microscope within 24 h to 1 week after extravasation and secondary wound closure. The second conservative approach involves daily saline dressing. The wound is then covered with split skin graft or flap. Necrosis of peripheral vessels and nerves of limb may need amputation. However, immediate intervention is indicated in case of non-resolving erythema, pain or swelling and presence of large skin defects. Few experimental animal and human studies have reported good results with the use of granulocyte macrophage colony stimulating factor (GM-CSF) in the management of ulcers in anthracycline extravasation[19,56,57,58,59].

• Physiotherapy: It is indicated in late complications (functional or neural loss of the limb), but is rare.


Extravasation is a dreaded complication of anticancer drugs and can be avoided through proper guidelines. Once extravasation occurs, tissue injury is inevitable but can be reduced with the proper antidote. All anticancer drugs should be infused by trained staff, and preferably in the oncology department only. The clinical textbooks should cite this complication and its management, so that primary clinical physicians are able to handle this complication in its golden hour.

Authors contribution

All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.

Competing interests

None declared.

Conflict of interests

None declared.


All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.


  • 1. Chabner BA, Amrein PC, Druker B, Michaelson D, Mitsiades CS, Goss PE. Antineoplastic agents. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gillman’s the pharmacological basis of therapeutics, 11th ed. USA: The McGraw-Hills Companies Inc 2006pp1315-1404.
  • 2. Chu E, Sartorelli AC. Cancer chemotherapy. In: Katzung BG, editor. Basic & clinical pharmacology. 10th ed. Singapore: The McGraw-Hill Companies Inc 2007pp878-907.
  • 3. Tripathi KD . Anticancer drugs. In: Essentials of medical pharmacology. 6th ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd 2008pp819-36.
  • 4. Bernstam FM, Pollock RE. Oncology. In: Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Dunn DL, Hunter JG, Pollock RE, et al., editors. Swartz’s manual of surgery. 8th edition. New York: The McGraw-Hills Companies Inc 2006pp183-215.
  • 5. Longo DL . Principles of cancer treatment. In: Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL, Jameson JL, et al., editors. Harrison’s principles of internal medicine. 17 ed. New York: The McGraw-Hills Companies Inc 2008.
  • 6. Foon KA, Geski LJ, Ghobrial I, Jacobs SA. The non-hodgkin lymphomas. In: Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, editors. Williamshematology. 7th ed. Singapore: The McGraw-Hills Companies Inc 2007.
  • 7. Payne S, Miles D. Mechanisms of anticancer drugs. In: Gleeson M, Browning G, Burton J, Clarke R, Hibbert J, Jones NS, et al., editors. Scott-Brown’s otolaryngology. Vol I, 7thed. London: Hodder Arnold 2008pp34-46.
  • 8. Thakur JS, Chauhan CG, Diwana VK, Chauhan DC, Thakur A. Extravasational side effects of cytotoxic drugs: a preventable catastrophe. Indian J Plast Surg 2008 Jul;41(2):145-50.
  • 9. Bertelli G . Prevention and management of extravasation of cytotoxic drugs. Drug Safety 1995 Apr;12(4):245-55.
  • 10. Dorr RT . Antidotes to vesicant chemotherapy extravasations. Blood Review 1990 Mar;4(1):41-60.
  • 11. Schulmeister L . Managing vesicant extravasations. Oncologist 2008 Mar;13(3):284-8.
  • 12. Dorr RT . Pharmacologic management of vesicant chemotherapy extravasations. In: Dorr RT, Vonn Hoff DD, editors. Cancer chemotherapy handbook, 2nd edition. Norwalk, CT: Appleton & Lange 1993pp109-18.
  • 13. Dorr RT, Dordal MS, Koenig LM, Taylor CW, McCloskey TM. High levels doxorubicin in the tissues of a patient experiencing extravasation during a 4-day infusion. Cancer 1999 Dec ;64(12):2462-4.
  • 14. Sonneveld P, Wassenaar HA, Nooter K. Long persistence of doxorubicin in human skin after extravasation. Cancer Treatment Rep 1984 Jun;68(6):895-896.
  • 15. Schrijvers DL . Extravasation: a dreaded complication of chemotherapy. Ann Oncol 2003;14(Supp 3):iii26-30.
  • 16. Herrington JD, Figueroa JA. Severe necrosis due to paclitaxel extravasation. Pharmacotherapy 1997 Jan–Feb;17(1):163-5.
  • 17. Burd DAR, Santis G, Milward TM. Severe extravasation injury: an avoidable iatrogenic disaster? BMJ. 1985 May;290(6481):1579-80.
  • 18. Alberts DS, Dorr RT. Case report: topical DMSO for Mitomycin C induced skin ulceration. Oncol Nurs Forum 1991 May–Jun;18(4):693-5.
  • 19. Eroglu E, Sari A, Altuntas I, Delibas N, Candir C, Agalar F. The effect of GM-CSF (granulocyte macrophage colony stimulating factor) on doxorubicin-induced tissue necrosis and wound healing. Indian J Cancer 2000 Dec;37(4):153-157.
  • 20. Jacobson JO, Polovich M, McNiff KK, Lefebvre KB, Cummings C, Galioto M. American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards. J Clin Oncol 2009 Nov;27(32):5469-75.
  • 21. Pérez Fidalgo JA, García Fabregat L, Cervantes A, Margulies A, Vidall C, Roila F. Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines. Eur J Oncol Nurs 2012 Dec;16(5):528-34.
  • 22. Schulmeister L . Preventing and managing vesicant chemotherapy extravasations. J Support Oncol 2010 Sept–Oct;8(5):212-5.
  • 23. Schulmeister L . Extravasation. In: Polovich M, Whitford JM, Olsen M, editors. Chemotherapy and biotherapy guidelines and recommendations for practice, 3rd ed. Pittsburgh: Oncology Nursing Society; 2009pp105-11.
  • 24. Ener RA, Meglathery SB, Styler M. Extravasation of systemic hemato-oncological therapies. Ann Oncol 2004 Jun;15(6):858-62.
  • 25. Olver IN, Aisner J, Hament A, Buchanan L, Bishop JF, Kaplan RS. A prospective study of topical dimethyl sulfoxide for treating anthracycline extravasation. J Clin Oncol 1988 Nov;6(11):1732-5.
  • 26. Bertelli G, Dini D, Forno GB, Gozza A, Silvestro S, Venturini M. Hyaluronidase as an antidote to extravasation to vinca alkaloids. J Cancer Res Clin Oncol 1994;120(8):505-6.
  • 27. Bertelli G, Gozza A, Forno GB, Vidili MG, Silvestro S, Venturini M. Topical dimethyl sulfoxide for the prevention of soft tissue injury after extravasation of vesicant drugs: a prospective clinical study. J ClinOncol 1995 Nov;13(11):2851-5.
  • 28. Dissa JJ, Chang RR, Mucci SJ, Goldberg NH. Prevention of adriamycin- induced -full thickness skin loss using hyaluronidase infiltration. PlastReconstr Surg 1998 Feb;101(2):370-4.
  • 29. Langer SW, Sehested M, Jensen PB. Treatment of anthracycline extravasation with dexrazoxane. Clin Cancer Res 2000;63680-6.
  • 30. Langer SW, Sehested M, Jensen PB, Buter J, Giaccone G. Dexrazoxane in anthracycline extravasation. J Clin Oncol 2000;18(16):3064.
  • 31. Laurie SW, Wilson KL, Kernahan DA, Bauer BS, Vistnes LM. Intravenous extravasation injuries: the effectiveness of hyaluronidase in their treatment. Ann Plast Surg 1984 Sept;13(3):191-4.
  • 32. Hasinoff BB, Schroeder PE, Patel D. Totec: anthracyline extravasation chemotherapy. .
  • 33. Dorr RT, Soble M, Alberts DS. Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse.Cancer ChemotherPharmacol. 1988;22(4):299-302.
  • 34. Hajaridadeh H, Lebredo L, Barrie R, Woltering EA. Protective effect of doxorubicin in vitamin C or dimethyl sulfoxide skin ulceration in pig. Ann SurgOncol 1994 Sept;1(5):411-4.
  • 35. Yilmaz M, Demirdover C, Mola F. Treatment options in extravasation injury: an experimental study in rats. PlastReconstr Surg 2002 Jun;109(7):2418-23.
  • 36. Lucero MJ, Vigo J, Rabasco AM, Sanchez JA, Martin F. Protection by alpha-tocopherol against skin necrosis induced by doxorubicin hydrochloride.Pharmazie. 1993 Oct;48(10):772-5.
  • 37. Svingen BA, Powis G, Appel PL, Scott M. Protection by alpha-tocopherol and dimethylsulfoxide (DMSO) against adriamycin induced skin ulcers in the rat. Res Commun Chem Pathol Pharmacol 1981 Sept;32(1):189-92.
  • 38. Bekerecioğ lu M, Kutluhan A, Demirtas I, Karaayvaz M. Prevention of adriamycin-induced skin necrosis with various free radical scavengers. J Surg Res 1998 Feb;75(1):61-5.
  • 39. Dorr RT, Alberts DS. Failure of DMSO and vitamin E to prevent doxorubicin skin ulceration in the mouse.Cancer Treat Rep. 1983 May;67(5):499-501.
  • 40. Ludwig CU, Stoll HR, Obrist R, Obrecht JP. Prevention of cytotoxic drug induced skin ulcers with dimethyl sulfoxide (DMSO) and alpha-tocopherole. Eur J Cancer Clin Oncol 1987 Mar;23(3):327-9.
  • 41. Askar I, Erbas MK, Gurlek A. Effects of heparin fractions on the prevention of skin necrosis resulting from adriamycin extravasation: an experimental study. Ann Plast Surg 2002 Sept;49(3):297-301.
  • 42. Kesik V, Kurt B, Tunc T, Citak EC, Kismet E, Koseoglu V. Melatonin ameliorates doxorubicin-induced skin necrosis in rats. Ann Plast Surg 2010 Aug;65(2):250-3.
  • 43. Aktas S, Toklu AS, Olgaç V. Hyperbaric oxygen therapy in adriamycin extravasation: an experimental animal study. Ann Plast Surg 2000 Aug;45(2):167-71.
  • 44. Scuderi N, Onesti MG. Antitumour agents: extravasation, management and surgical treatment. Ann Plast Surg 1994 Jan;32(1):39-44.
  • 45. Langer SW, Thougaard AV, Sehested M, Jensen PB. Treatment of anthracycline extravasation in mice with dexrazoxane with or without DMSO and hydrocortisone. Cancer Chemother Pharmacol 2006 Jan;57(1):125-8.
  • 46. Gault DT . Extravsation injuries. Br J Plast Surg 1993 Mar;46(2):91-6.
  • 47. Steinmann G, Charpentier C, O’Neill TM, Bouaziz H Mertes. Liposuction and extravasation injuries in ICU. BJA 2005 Sept;95(3):355-7.
  • 48. Hankin FM, Louis DS. Surgical management of doxorubicin (adriamycin) extravasation. J Pediatr Orthop 1984 Jan;4(1):96-9.
  • 49. Larson DL . What is the appropriate management of tissue extravasation by antitumor agents? PlastReconstr Surg. 1985 Mar;75(3):397-405.
  • 50. Rudolph R, Larson DL. Aetiology and treatment of chemotherapeutic agent extravasation injuries: a review.J ClinOncol. 1987 July;5(7):1116-26.
  • 51. Tsavaris NB, Karagiaouris P, Tzannou I, Komitsopoulou P, Bacoyiannis C, Karabellis A. Conservative approach to the treatment of chemotherapy-induced extravasation. J Dermatol Surg Oncol 1990 Jun;16(6):519-22.
  • 52. Andersonn AP, Dahlstrom KK. Clinical results after doxorubicin extravasation treated with excision guided by fluorescence microscopy. Eur J Cancer 1993;29A1712-4.
  • 53. Shenaq SM, Abbase EH, Friedman JD. Soft-tissue reconstruction following extravasation of chemotherapeutic agents.SurgOncolClin N Am. 1996 Oct;5(4):825-45.
  • 54. Heitmann C, Durmus C, Ingianni G. Surgical management after doxorubicin and epirubicin extravasation. J Hand Surg (Br) 1998 Oct;23(5):666-8.
  • 55. Cedidi C, Hierner R, Berger A. Plastic surgical management in tissue extravasation of cytotoxic agents in the upper extremity. Eur J Med Res 2001 Jul;6(7):309-14.
  • 56. Langstein HN, Duman H, Seeling D, Butler CE, Evans GR. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plast Surg 2002 Oct;49(4):369-74.
  • 57. Ulutin HC, Guden M, Dede M, Pak Y. Comparison of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in the treatment of chemotherapy extravasation ulcers. Eur J Gynaecol Oncol 2000;21613-5.
  • 58. Vargel I, Erdem A, Ertoy D, Pinar A, Erk Y, Altundag MK, Gullu I. Effects of growth factors on doxorubicin-induced skin necrosis: documentation of histomorphological alteration and early treatment by GM-CSF and G-CSF. Ann Plast Surg 2002 Dec;49(6):646-53.
  • 59. Schneider SM, Distelhorst CW. Chemotherapy induced emergencies. Semin Oncol 1989 Dec;16(6):572-8.
Licensee to OAPL (UK) 2013. Creative Commons Attribution License (CC-BY)

Vesicant and irritant chemotherapeutic drugs

Vesicant drugs Irritant drugs
Alkylating agents (DNA-Binding): Mechlorethamine (MustineHCl)** Alkylating agents: Cyclophosphamide, Ifosfamide, Melphalan, Carmustine, Dacarbazine, Thiothepa
Antitumour antibiotics (Anthracyclines, DNA-Binding)**: Mitomycin C, Daunorubicin (Rubidomycin), Doxorubicin (Adriamycin), Epirubicin, Idarubicin, Actinomycin D (Dactinomycin) Antimetabolites: Methotrexate, 5-Fluorouracil (5-FU)*, Cytarabine (Cytosine arabinoside), Fludarabine, Gemcitabine
Vinca alkaloids (Non-DNA Binding)**: Vincristine (Oncovin), Vinblastine, Vinorelbine Antitumour antibiotic: Bleomycin
Taxanes (Non-DNA Binding)*: Docetaxel, Paclitaxel Epipodophyllotoxin: Etoposide*
Platinum analogs: Cisplatin*, Carboplatin, Oxaliplatin*

** Highly vesicant, * Low vesicant.