antibiotics plant alkaloids

Question 1

doxorubicin

Answer 1

antracyclines an antitumor antibiotics

Question 2

irinotecan, topotecan

Answer 2

topo I inhibitor- plant alkaloids

Question 3

vinCRistine, vinBLastine, vinorelbine

Answer 3

vinca alkaloids- plant alkaloids

Question 4

paclitaxel, docetaxel

Answer 4

taxanes- plant alkaloids

Question 5

A streptomycin compound was a precursor to _________, named rubidomycin, which became doxorubicin.

Answer 5

anthracyclines

Question 6

The pharmacologic activity of these agents is qualitatively similar. Un-ionized drug enters the cell via passive diffusion, and localizes to the _________.

Nucleated cells can rapidly accumulate the drug. __________ intercalate between DNA base pairs, forming links between DNA strands, causing torsional stress on DNA, leading to damage and breakage.

_________ tends to favor binding in dGdC-rich regions of the DNA while __________has highest affinity for 5’-TCA.

This binding can cause DNA stiffening, bending and elongation, which may ultimately lead to decreased ability of DNA to _________.

Answer 6

The pharmacologic activity of these agents is qualitatively similar. Un-ionized drug enters the cell via passive diffusion, and localizes to the nucleus.

Nucleated cells can rapidly accumulate the drug. Anthracyclines intercalate between DNA base pairs, forming links between DNA strands, causing torsional stress on DNA, leading to damage and breakage.

Daunorubicin tends to favor binding in dGdC-rich regions of the DNA while doxorubicin has highest affinity for 5’-TCA.

This binding can cause DNA stiffening, bending and elongation, which may ultimately lead to decreased ability of DNA to replicate.

Question 7

A more important mechanism of tumor cell killing is inhibition of _________, an enzyme present in all cells that produces nicks in double stranded DNA to relieve torsional strain.

The ___________complex is referred to as the “cleavable complex.”

This nicking process allows DNA to unwind and proceed with replication, and ____then helps to re-ligate the strands upon completion.

___________ bind the cleavable complex and disrupt DNA replication. This mechanism is also likely responsible for secondary malignancies that can occur, such as leukemias.

Answer 7

A more important mechanism of tumor cell killing is inhibition of topoisomerase II (topo II), an enzyme present in all cells that produces nicks in double stranded DNA to relieve torsional strain.

The DNA/Topo II complex is referred to as the “cleavable complex.”

This nicking process allows DNA to unwind and proceed with replication, and topo II then helps to re-ligate the strands upon completion.

Anthracyclines bind the cleavable complex and disrupt DNA replication. This mechanism is also likely responsible for secondary malignancies that can occur, such as leukemias.

Question 8

The majority of these drugs are cleared via the __________ system.

Care should be taken when dosing in patients with elevated _____ and dose adjustment may be required.

Answer 8

The majority of these drugs are cleared via the biliary system.

Care should be taken when dosing in patients with elevated bilirubin, and dose adjustment may be required.

Question 9

One of the major dose-limiting side effects of the anthracyclines is ________.

All cell lines are affected, but ______ is most problematic.
Occurring 7-10 days after dosing, and most cases resolve by day 14.

Patients receiving anthracyclines will develop ______.

Answer 9

One of the major dose-limiting side effects of the anthracyclines is myelosuppression.

All cell lines are affected, but neutropenia is most problematic. Neutropenia occurs 7-10 days after dosing, and most cases resolve by day 14.

Patients receiving anthracyclines will develop alopecia.

Question 10

Anthracyclines are ________(with the exceptions of the liposomal formulations of doxorubicin/doxil).

Drug extravasation may lead to severe ___________, sometimes necessitating plastic surgery.

To prevent extravasation, special care is used to administer ________. All infusion must go through a newly placed peripheral IV or a central catheter, and placement in a vein must be confirmed.

If extravasation occurs, what is the treatment?

Answer 10

Anthracyclines are vesicants (with the exceptions of the liposomal formulations of doxorubicin).

Drug extravasation may lead to severe tissue necrosis, sometimes necessitating plastic surgery. To prevent extravasation, special care is used to administer vesicants. All infusion must go through a newly placed peripheral IV or a central catheter, and placement in a vein must be confirmed.

If extravasation occurs, there are few antidotes, and treatment is mainly supportive care.

Question 11

Anthracyclines are considered moderately to highly emetogenic, causing __________

_________ is also known to cause delayed nausea and vomiting, requiring scheduled anti-emetics post-treatment.

Answer 11

Anthracyclines are considered moderately to highly emetogenic, causing acute nausea/vomiting.

Doxorubicin is also known to cause delayed nausea and vomiting, requiring scheduled anti-emetics post-treatment.

Question 12

Anthracyclines, with the exception of mitoxantrone, have a ______color, which may cause urine discoloration.

Mitoxantrone has a ____ color which can cause a patient’s urine to turn ________

Answer 12

Anthracyclines, with the exception of mitoxantrone, have a red color, which may cause urine discoloration. Mitoxantrone has a blue color which can cause a patient’s urine to turn greenish-blue.

Question 13

There are other mechanisms of action for these agents. The exact contribution each plays in tumor cell killing is unknown. ‘
The anthracyclines undergo 1 and 2 electron reductions (semiquinones) that turn the agents into _______________ (semiquinones + oxygen = ), which in turn can cause damage to lipid membranes, intracellular macromolecules and DNA.

_________ formation leads to peroxidation of the tumor cell membranes.

Answer 13

There are other mechanisms of action for these agents. The exact contribution each plays in tumor cell killing is unknown.

The anthracyclines undergo 1 and 2 electron reductions that turn the agents into reactive oxygen species, which in turn can cause damage to lipid membranes, intracellular macromolecules and DNA.

Superoxide formation leads to peroxidation of the tumor cell membranes.

Question 14

Anthracyclines can slowly release iron from ferritin to form iron/anthracycline complexes that __________.

This may be important in the unique ____________ associated with these drugs.

_________ also has decreased levels of enzymes involved in anti-oxidant defense, limiting the ability to handle free oxygen radicals.

Answer 14

Anthracyclines can slowly release iron from ferritin to form iron/anthracycline complexes that intercalate DNA.

This may be important in the unique cardiotoxicity associated with these drugs.

Cardiac tissue also has decreased levels of enzymes involved in anti-oxidant defense, limiting the ability to handle free oxygen radicals.

Question 15

Cardiotoxicity from anthracyclines is likely due to ?

_______is more susceptible due to decreased endogenous anti-oxidant defenses such as glutathione.

Answer 15

mitochondrial and cell membrane damage caused by reactive oxygen species binding iron and producing iron/anthracycline free radicals.

Myocardium is more susceptible due to decreased endogenous anti-oxidant defenses such as glutathione.

Question 16

Two distinct types of cardiotoxicity can occur with anthracycline administration.

The first is an ____________ that may occur after any dose, resulting in an MI-type clinical picture with acute EKG changes (ST segment changes, QTc prolongation and arrhythmias). Treatment is symptomatic and the anthracycline should not be administered to the patient again. It is impossible to predict who will get this toxicity and when, though it is rare.

____________ is more common, resulting from higher cumulative doses of the drug. The clinical picture is one of ____. Patients have decreased ejection fraction, dilatation of the heart, pulmonary/venous congestion and pleural effusions. This type of toxicity is reversible/irreversible and treated symptomatically.

Answer 16

Two distinct types of cardiotoxicity can occur with anthracycline administration.

The first is an acute idiosyncratic reaction that may occur after any dose, resulting in an MI-type clinical picture with acute EKG changes (ST segment changes, QTc prolongation and arrhythmias). Treatment is symptomatic and the anthracycline should not be administered to the patient again. It is impossible to predict who will get this toxicity and when, though it is rare.

Chronic cardiotoxicity is more common, resulting from higher cumulative doses of the drug. The clinical picture is one of congestive heart failure. Patients have decreased ejection fraction, dilatation of the heart, pulmonary/venous congestion and pleural effusions. Chronic cardiotoxicity is irreversible and treated symptomatically.

Question 17

Chronic cardiotoxicity is dose-

Answer 17

Chronic cardiotoxicity is dose-dependent.

When total cumulative doses exceed these thresholds, the patient is at increased risk for chronic cardiotoxicity. Some patients may be able to exceed these thresholds and have no adverse effects while others may develop cardiotoxicity at lower doses than those listed. Cardiac function is carefully monitored during anthracycline therapy.

Question 18

Various methods have been tried to help reduce the incidence of cardiotoxicity.

They include the use of (3).

______ such as dexrazoxan agents must be given within 30 minutes of doxorubicin, when the free radicals are being formed, to be effective.

Weekly doses, compared to those done every three weeks, are given as smaller doses over a shorter time in order to ______ high peak concentrations.

Answer 18

Various methods have been tried to help reduce the incidence of cardiotoxicity.

They include the use of chelating agents, liposomal formulations of the drug and manipulating infusional administration of the anthracyclines.

Chelating agents such as dexrazoxan must be given within 30 minutes of doxorubicin, when the free radicals are being formed, to chelate them and be effective.

Weekly doses, compared to those done every three weeks, are given as smaller doses over a shorter time in order to decrease high peak concentrations.

Question 19

One chelating agent, ______, protects against cardiotoxicity for patients receiving anthracyclines, though is only FDA-approved for women with breast cancer who have received over 300 mg/m2 doxorubicin.

It is hydrolyzed intracellularly by enzymatic and non-enzymatic mechanisms to yield an _________ derived analog.

It also strips iron from doxorubicin-iron complexes to decrease _____________.

Timing of administration is key, and must be within 30 minutes of receiving doxorubicin to chelate free radicals.

There is potential that __________ could protect tumor cells from anthracycline effects, therefore its use is limited.

Dose is ___:___ dexrazoxan:doxorubicin

Answer 19

One chelating agent, dexrazoxane, protects against cardiotoxicity for patients receiving anthracyclines, though is only FDA-approved for women with breast cancer who have received over 300 mg/m2 doxorubicin.

The drexrazoxane is hydrolyzed intracellularly by enzymatic and non-enzymatic mechanisms to yield an EDTA- derived analog.

It also strips iron from doxorubicin-iron complexes to decrease free radical formation.

Timing of administration is key, and must be within 30 minutes of receiving doxorubicin to chelate free radicals.

There is potential that dexrazoxane could protect tumor cells from anthracycline effects, therefore its use is limited.

Dose is 10:1 dexrazoxan:doxorubicin

Question 20

It is unclear if the side effects of dexrazoxane are due to the drug alone or due to concomitant anthracycline that is given.

Major side effects include (4)

Dexrazoxane is not used often, only in specific situations such as metastatic breast cancer.

Answer 20

It is unclear if the side effects of dexrazoxane are due to the drug alone or due to concomitant anthracycline that is given.

Major side effects include severe (1) nausea/vomiting (a serotonin inhibitor and steroid may be used for prophylaxis), (2) myelosuppression (mainly neutropenia), (3) alopecia and (4) mucositis.

Dexrazoxane is not used often, only in specific situations such as metastatic breast cancer.

Question 21

Liposomal products were developed to reduce the risk of ________.

High peak concentrations are ________due to the slower release of liposomal formulations, and _________ uptake by normal tissues may reduce __________.

However, it is unclear from studies if this is the case, and it is difficult to come up with equivalent dose when compared to other anthracyclines.

Answer 21

Liposomal products were developed to reduce the risk of cardiotoxicity.

High peak concentrations are decreased due to the slower release of liposomal formulations, and decreased uptake by normal tissues may reduce cardiotoxicity.

However, it is unclear from studies if this is the case, and it is difficult to come up with equivalent dose when compared to other anthracyclines.

Question 22

1. slow release of drug; reduces high peak concentrations
2. altered biodistribution
   enhance drug
3. accumulation in tumors

Answer 22

Doxil a liposome

Question 23

Resistance is mediated by multiple mechanisms.

The best understood is active efflux of drug via the _________.

This gene codes for a __________ membrane pump that actively pumps toxins out of cells.

Since cells view chemo as toxic, tumor cells up-regulate _____.

Some drugs are being developed to decrease the action of the ____ pump.

The danger of this is that conventional doses have been determined by patients with normally functional ____ pumps, so decreasing _______ activity may increase toxicity potential of chemotherapy drugs.

Tumor cells may also have altered topo II expression, which would make anthracyclines less effective. Tumor cells may also increase expression of glutathione and glutathione-dependent proteins, which would decrease anthracycline activity.

Answer 23

Resistance is mediated by multiple mechanisms.

The best understood is active efflux of drug via the multidrug resistance gene (MDR).

This gene codes for a 170kDa glycoprotein membrane pump that actively pumps toxins out of cells.

Since cells view chemo as toxic, tumor cells up-regulate MDR.

Some drugs are being developed to decrease the action of the MDR pump.

The danger of this is that conventional doses have been determined by patients with normally functional MDR pumps, so decreasing MDR activity may increase toxicity potential of chemotherapy drugs.

Tumor cells may also have altered topo II expression, which would make anthracyclines less effective. Tumor cells may also increase expression of glutathione and glutathione-dependent proteins, which would decrease anthracycline activity.

Question 24

Daunorubicin and idarubicin are used for _________, while doxorubicin and epirubicin are used more for ________.

Answer 24

Daunorubicin and idarubicin are used for leukemias, while doxorubicin and epirubicin are used more for solid tumors.

Question 25

Anthracycline medication for Wilm’s tumor, Ewing’s sarcoma, germ cell tumors

Answer 25

dactinomycin

Question 26

Anthracyclin medication for Hodgkin’s disease, sclerosing agent for pleural effusions; Lung toxicity

Answer 26

bleomycin

Question 27

Anthracyclin medication for Bladder cancer, anal cancer; Long nadir (4-6 weeks)

Answer 27

mitomycin- C

Question 28

____________, plant alkaloids, were derived from the Camptotheca acuminata tree as part of the NCI initiative to find anti-cancer drugs from natural products.

Alkaloid activity was discovered in the late 1950s/early 1960s, but the drug was abandoned because of severe toxicity seen in early trials.

Unpredictable and serious _____ toxicity halted use in early phase I trials. There was renewed interest in the late 1980s when a more ________ form with less toxicity was discovered.

Answer 28

Camptothecins, plant alkaloids, were derived from the Camptotheca acuminata tree as part of the NCI initiative to find anti-cancer drugs from natural products.

Alkaloid activity was discovered in the late 1950s/early 1960s, but the drug was abandoned because of severe toxicity seen in early trials.

Unpredictable and serious GI toxicity (severe diarrhea) halted use in early phase I trials. There was renewed interest in the late 1980s when a more water-soluble form with less toxicity was discovered.

Question 29

plant alakloids activity of the agents is ____, with the S-isomer being much more potent.

Answer 29

stereospecific

Question 30

Camptothecins are cell cycle-specific drugs, working during the ____-phase of the life cycle.

The toxic effects of the camptothecins are due to inhibition of ____________ an enzyme ubiquitous in all cells.

It that functions to relax supercoiled DNA by creating transient single-strand nicks to allow unwinding for DNA replication and RNA transcription.

_________ promotes movement of the replication fork and provides genomic stability. Once DNA replication is complete, _____ re-ligates the DNA strands.

The ________complex is referred to as the “cleavable complex.”

Answer 30

Camptothecins are cell cycle-specific drugs, working during the S-phase of the life cycle.

The toxic effects of the camptothecins are due to inhibition of topoisomerase I (topo I), an enzyme ubiquitous in all cells.

It that functions to relax supercoiled DNA by creating transient single-strand nicks to allow unwinding for DNA replication and RNA transcription.

Topo I promotes movement of the replication fork and provides genomic stability. Once DNA replication is complete, topo I re-ligates the DNA strands.

The topo I/DNA complex is referred to as the “cleavable complex.”

Question 31

Camptothecins MOA

Answer 31

bind to the cleavable complex, disrupting re-ligation and resulting in DNA with multiple nicks, which ultimately terminates DNA synthesis and leads to cell death.

Question 32

topo 1 inhibitors: (2) and for what cancer

Answer 32

1. topotecan- ovarian cancer

2. irinotecan- GI cancer

Question 33

Both topotecan and irinotecan have poor _____ and are given intravenously.

Topotecan has no _______

Major toxicities include (4)

Answer 33

Both topotecan and irinotecan have poor oral bioavailability and are given intravenously.

Topotecan has no active metabolite.

Major toxicities include (1) myelosuppression, both (2) neutropenia and (3) thrombocytopenia, and (4) GI (N/V, mucositis and diarrhea).

Question 34

Irinotecan is a pro-drug, metabolized by _________ to a much more potent active metabolite (SN-38).

Two significant side effects are associated with irinotecan use.

(1) _____________ may be dose limiting in some instances, primarily manifested as neutropenia/ thrombocytopenia/eosinophilia order that they are most likely to occur.

Onset is ____days after administration, with resolution and count recovery in 14-22 days.

(2) The other major dose-limiting side effect associated with irinotecan is ___________

There are two types of associated with this drug.

(a) An _______________ presents with cramping and abdominal pain during or shortly after infusion. This is thought to be due to a _________ effect, with irinotecan inhibiting acetylcholinesterase a proposed mechanism. Treatment for this early onset diarrhea is _________, typically given at a dose of 0.25 mg.

(b) More common is a__________ that occurs within 5-14 days of irinotecan administration. Patients experience frequent, severe watery stools, which may lead to dehydration and electrolyte abnormalities that can be fatal. The exact mechanism is unknown, but may be attributable to activity of the __________metabolite.
All patients receiving irinotecan should be sent home with a prescription for _________, which should be taken at the first sign of diarrhea and continued until the diarrhea has stopped for at least 12 hours. which is another drug that could be used?

Other side effects include nausea, vomiting, alopecia, asthenia (sensation of weakness, but when actually tested, muscle strength is fine), anorexia, fatigue, elevated transaminases and bilirubin and dermatological reactions. There are no specific treatments other than supportive care as indicated.
_______ is rare, and happens more often in patients with lung cancer and underlying lung pathology.

Answer 34

Irinotecan is a pro-drug, metabolized by carboxyl esterase to a much more potent active metabolite (SN-38).

Two significant side effects are associated with irinotecan use.

(1) Myelosuppression may be dose limiting in some instances, primarily manifested as neutropenia> thrombocytopenia>eosinophilia.

Onset is 6-12 days after administration, with resolution and count recovery in 14-22 days.

(2)The other major dose-limiting side effect associated with irinotecan is diarrhea.

There are two types of diarrhea associated with this drug.

(a) An early-onset diarrhea presents with cramping and abdominal pain during or shortly after infusion. This is thought to be due to a cholinergic effect, with irinotecan inhibiting acetylcholinesterase a proposed mechanism. Treatment for this early onset diarrhea is atropine, typically given at a dose of 0.25 mg.

(b) More common is a late-onset diarrhea that occurs within 5-14 days of irinotecan administration. Patients experience frequent, severe watery stools, which may lead to dehydration and electrolyte abnormalities that can be fatal. The exact mechanism is unknown, but may be attributable to activity of the SN-38 metabolite.
All patients receiving irinotecan should be sent home with a prescription for loperamide, which should be taken at the first sign of diarrhea and continued until the diarrhea has stopped for at least 12 hours. Octreotide (a somatostatin analog that inhibits release of serotonin and other GI-acting peptides) is an alternative agent if loperamide is not effective or not tolerated.

Other side effects include nausea, vomiting, alopecia, asthenia (sensation of weakness, but when actually tested, muscle strength is fine), anorexia, fatigue, elevated transaminases and bilirubin and dermatological reactions. There are no specific treatments other than supportive care as indicated.
________ is rare, and happens more often in patients with lung cancer and underlying lung pathology.

Question 35

Topo I inhibitro resistance

1. two outcomes due to the actions of increased MDR gene
2. reduced levels of carboxyl esterase leads to (2)

Non-cycling cells are also relatively resistant to the effects _________

Answer 35

1. increased MDR activity leads to a reduction of the drug intracellular leading to (a) reduced drug accumulation (b) altered intracellular drug distribution into the nucleus
2. reduced levels of carboxyl esterase activity can lead to (a) decreased levels of the active metabolite SN38 (b) decreased transcription of topo I enzymes leading to decreased target for drug binding

Non-cycling cells are also relatively resistant to the effects of topo I inhibitors.

Question 36

1. Found in small quantities in pink periwinkle plant
2. Used originally for toothaches, healing wounds, diabetes
3. Screened for use as anti-diabetic agent

Answer 36

vinca alkaloids

Question 37

The major mechanism of action of vinca alkaloids is

other mechanisms probably involve: (3)

Answer 37

disruption of microtubules. Specifically, they bind tubulin and inhibit tubulin polymerization, thus preventing formation of the mitotic spindle and leading to mitotic arrest.

other mechanisms probably involve:

1. Inhibition DNA, RNA, protein synthesis
2. Disruption lipid metabolism
3. Inhibition of glycolysis

Question 38

In Vincas,
The major toxicity profile difference is between __________; __________shares almost all of the toxicities of both.

The major toxicity associated with _______ is neurotoxicity, which presents as peripheral neuropathy in a stocking/glove paresthesia. Patients can also have decreased autonomic function, resulting in constipation ranging from mild to a paralytic ileus. Concurrent use of appropriate laxative regimens is key. Patients at greatest risk for developing neuropathy are those with pre-existing neuropathy (i.e. diabetics).

The major side effect associated with _________ is myelosuppression, with neutropenic nadir occurring rapidly (4-6 days after dosing).

_______ has little effect on the bone marrow.

Answer 38

The major toxicity profile difference is between vincristine and vinblastine; vinorelbine shares almost all of the toxicities of both.

The major toxicity associated with vinCristine is neurotoxicity, which presents as peripheral neuropathy in a stocking/glove paresthesia. Patients can also have decreased autonomic function, resulting in constipation ranging from mild to a paralytic ileus. Concurrent use of appropriate laxative regimens is key. Patients at greatest risk for developing neuropathy are those with pre-existing neuropathy (i.e. diabetics).

The major side effect associated with vinBlastine is myelosuppression, with neutropenic nadir occurring rapidly (4-6 days after dosing).

VinCristine has little effect on the bone marrow.

Question 39

Vinca used primarily for hematological malignancies such as non-Hodgkin’s lymphoma and ALL;

Answer 39

Vincristine

Question 40

Vinca used used for Hodgkin’s lymphoma and testicular cancer

Answer 40

vinblastine

Question 41

Vinca used mostly used for solid tumors such as breast cancer and non-small cell lung cancer.

Answer 41

vinorelbine

Question 42

The final group of alkaloids are the taxanes, which are also ____-phase specific drugs targeting cells in active mitosis.

These substances were isolated from the Yew tree. Paclitaxel (Taxol) was originally isolated from the bark of the western Yew (Taxus brevifolia) while docetaxel (Taxotere) was isolated from the needles of the European Yew tree. Taxanes are now semisynthetic.

Their major mechanism of action is promotion of ____________, enhancing the action of tubulin dimers, stabilizing existing microtubules and _____ disassembly. This causes cells to arrest in ___ phase, inhibiting cell division and causing cell death.

Resistance to taxanes is mediated by the _____ gene, which pumps the drug out of the cell, and through alterations in tubulin that cause decreased drug binding.

Answer 42

The final group of alkaloids are the taxanes, which are also M-phase specific drugs targeting cells in active mitosis.

These substances were isolated from the Yew tree. Paclitaxel (Taxol) was originally isolated from the bark of the western Yew (Taxus brevifolia) while docetaxel (Taxotere) was isolated from the needles of the European Yew tree. Taxanes are now semisynthetic.

Their major mechanism of action is promotion of microtubule formation, enhancing the action of tubulin dimers, stabilizing existing microtubules and inhibiting disassembly. This causes cells to arrest in M phase, inhibiting cell division and causing cell death.

Resistance to taxanes is mediated by the MDR gene, which pumps the drug out of the cell, and through alterations in tubulin that cause decreased drug binding.

Question 43

A major toxicity associated with taxanes is __________, often warranting prophylactic use of myeloid growth factors.

_________ are also common with these drugs, usually presenting in a stocking/glove distribution and associated with high cumulative doses and multiple cycles of treatment.

why are taxanes associated with infusion-related toxicities, characterized by flushing, erythema, hypotension, dyspnea and/or bronchospasms, and require pre-medication with steroids and histamine blockers?

A unique side effect of docetaxel is __________ (palmar-plantar erythrodysesthesia). The exact mechanism of this is unknown; patients present with a painful rash on palms/soles that may progress to desquamation.

Docetaxel is also associated with a___________, with weight gain, edema, pleural effusions, and ascites, for which corticosteroids may be prophylactic.

Taxanes are primarily used in the treatment of several solid tumors, including

Answer 43

A major toxicity associated with taxanes is myelosuppression (neutropenia), often warranting prophylactic use of myeloid growth factors.

Peripheral neuropathies are also common with these drugs, usually presenting in a stocking/glove distribution and associated with high cumulative doses and multiple cycles of treatment.
Taxanes are complex, large structures that are not very soluble, and must be solubilized with toxic substances (such as Cremophor EL, a polyoxyethylated castor oil) for intravenous injection. Therefore taxanes may cause infusion-related toxicities, characterized by flushing, erythema, hypotension, dyspnea and/or bronchospasms, and require pre-medication with steroids and histamine blockers.

A unique side effect of docetaxel is hand-foot syndrome (palmar-plantar erythrodysesthesia). The exact mechanism of this is unknown; patients present with a painful rash on palms/soles that may progress to desquamation. Docetaxel is also associated with a fluid retention syndrome, with weight gain, edema, pleural effusions, and ascites, for which corticosteroids may be prophylactic.

Taxanes are primarily used in the treatment of several solid tumors, including breast, lung and ovarian cancers, often in combination with other chemotherapeutic agents.