3

Guidelines for
Chemotherapy and
Dosing Modifications
Vanita Noronha, Augusto Mota, Miklos Fogarasi,
Dawn Tiedemann, and Edward Chu

Successful administration of chemotherapy relies on several critical fac-

tors, including the patient’s age; performance status; co-morbid illnesses;
and baseline hematologic, hepatic, and renal status. The dose of a given
chemotherapeutic agent must be adjusted accordingly to reflect these pa-
rameters, as well as any specific drug-induced toxicities that may have
been experienced with prior treatment. This chapter outlines perfor-
mance scales that have been established to determine a patient’s func-
tional status; reviews methods to determine creatinine clearance, body
surface area, and drug dose; and provides recommendations for dosing
in the setting of myelosuppression, hepatic dysfunction, and renal dys-
function. General guidelines for dialyzing chemotherapeutic agents in
the setting of drug overdose or renal failure are provided, and the extrav-
asation potential of various agents is reviewed. A more detailed review for
each individual drug is provided in Chapter 2, and the reader is advised
to refer to the published literature for further details regarding specific
guidelines for drug precautions and dose modifications.

Guidelines for Chemotherapy and Dosing Modifications 375

 Table 1. Performance Scales
Karnofsky
(%) Performance
100 Normal, no evidence of disease
90 Able to carry on normal activity, minor signs or symptoms of
disease
80 Normal activity with effort, some signs or symptoms of
disease
70 Unable to perform normal activity, cares for self
60 Requires occasional assistance
50 Requires considerable assistance and frequent medical care
40 Disabled, requires special care and assistance
30 Severely disabled, hospitalization may be required
20 Hospitalization necessary for support, very sick
10 Moribund, rapid progression of disease
0 Dead

ECOG
(%) Performance
0 Asymptomatic, normal activity
1 Fully ambulatory, symptomatic, able to perform activities of
daily living
2 Symptomatic, up and about, in bed less than 50% of time
3 Symptomatic, capable of only limited self-care, in bed more
than 50% of time
4 Completely disabled, cannot perform any self-care,
bedridden 100% of time
5 Dead

376 Physicians’ Cancer Chemotherapy Drug Manual

Table 2. Determination of Creatinine
Clearance
• The creatinine clearance is determined by the Cockcroft-Gault formula
(Cockcroft, DW, Gault, MH. Nephron 1976; 16: 31–34), which takes into
account age, weight, and serum creatinine.
weight (kg) × (140-age)
Males: Creatinine Clearance (mL/min) = 72 × serum creatinine (mg/dL)

weight (kg) × (140-age) × 0.85

Females: Creatinine Clearance (mL/min) = 72 × serum creatinine (mg/dL)
• The creatinine clearance can also be determined from a timed urine
collection.
urine creatinine
Creatinine Clearance = × urine volume
serum creatinine time

Table 3. Determination of Target Area

Under the Curve (AUC)
The area under AUC refers to the area under the drug concentration ×
time curve, and it provides a measure of total drug exposure. It is ex-
pressed in concentration × units (mg/mL × min).
A formula for quantifying exposure to carboplatin based on dose and re-
nal function was developed by Calvert et al. (Calvert, H, et al. J Clin Oncol
1989;7:1748–1756) and is as follows:
Carboplatin Dose (mg) = target AUC (mg/mL × min) × [GFR (mL/min)
+ 25]
It is important to note that the total dose is in mg and NOT mg/m2. Tar-
get AUC is usually between 5 and 7 mg/mL/min for previously untreated
patients. In previously treated patients, lower AUCs (between 4 and
6 mg/mL/min) are recommended. AUCs > 7 are generally not associ-
ated with improved response rates.

Table 4. Determination of Drug Dose

• Drug doses are calculated according to body surface area (BSA,
mg/m2).
• BSA is typically determined by using a nomogram scale or by using a
BSA calculator.
• Once the BSA is determined, multiply the BSA by the amount of drug
specified in the regimen to give the total dose of drug to be
administered.

Guidelines for Chemotherapy and Dosing Modifications 377

 • For obese patients, ideal body weight (IBW), as opposed to the actual
body weight, may be used to calculate BSA. It is important to refer to
an IBW table to determine the IBW based on the individual’s actual
height. Once the IBW is determined, add one-third of the IBW to the
IBW, which is then used to determine the BSA.
• IBW can be calculated from the following formulas:
IBW for men (kg): 50.0 kg + 2.3 kg per inch over 5 feet
IBW for women (kg): 45.5 kg + 2.3 kg per inch over 5 feet
Taken from: Olin B (Ed): “Drug Facts and Comparisons” St. Louis, Missouri, 1996.

Table 5. Calculation of Body Surface

Area in Adult Amputees
Body Part % Surface Area of Amputated Part
Hand and 5 fingers 3.0
Lower part of arm 4.0
Upper part of arm 6.0
Foot 3.0
Lower part of leg 6.0
Thigh 12.0
BSA (m2) = BSA - [(BSA) × (%BSApart)], where BSA = body surface area, BSApart =
body surface area of amputated part.

Taken from: Colangelo, PM, et al. Am J Hosp Pharm 1984;41:2650–2655.

Table 6. General Guidelines for

Percentage of Chemotherapy
Dosage Based on Hematologic
Parameters
Granulocytes (× 106 cells)
Platelets > 2.0 1.5–1.99 1–1.49 < 1.0
> 100,000 100.0 75.0 50.0 0.0
50,000–99,000 50.0 50.0 50.0 0.0
< 50,000 0.0 0.0 0.0 0.0

378 Physicians’ Cancer Chemotherapy Drug Manual

Table 7. General Guidelines for
Chemotherapy Dosage Based on
Hepatic Function
Drug Recommended Dose Reduction for Hepatic Dysfunction
Alemtuzumab N/A
Altretamine No dose reduction is necessary.
Amifostine No dose reduction is necessary.
Aminoglutethimide No dose reduction is necessary.
Amsacrine Reduce dose by 25% if bilirubin > 2.0 mg/dL.
Anastrozole No formal recommendation for dose reduction.
Dose reduction may be necessary in patients
with hepatic dysfunction.
Arsenic trioxide No dose reduction is necessary.
L-Asparaginase No dose reduction is necessary.
Bicalutamide No formal recommendation for dose reduction.
Dose reduction may be necessary if bilirubin
> 3.0 mg/dL.
Bleomycin No dose reduction is necessary.
Buserelin No dose reduction is necessary.
Busulfan No dose reduction is necessary.
Capecitabine No dose reduction is necessary.
Carboplatin No dose reduction is necessary.
Carmustine No dose reduction is necessary.
Chlorambucil No dose reduction is necessary.
Cisplatin No dose reduction is necessary.
Cladribine No dose reduction is necessary.
Cyclophosphamide Reduce by 25% if bilirubin 3.0–5.0 mg/dL or
SGOT > 180 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Cytarabine No formal recommendation for dose reduction.
Dose reduction may be necessary in patients
with hepatic dysfunction.
Dacarbazine No dose reduction is necessary.
Dactinomycin Reduce dose by 50% if bilirubin > 3.0 mg/dL.
Daunorubicin Reduce dose by 25% if bilirubin 1.5–3.0 mg/dL.
Reduce dose by 50% if bilirubin > 3.0 mg/dL.
Omit if bilirubin > 5.0 mg/dL.

Guidelines for Chemotherapy and Dosing Modifications 379

 Table 7. (cont)

Drug Recommended Dose Reduction for Hepatic Dysfunction

Docetaxel Omit if bilirubin > 1.5 mg/dL, SGOT
> 60 mg/dL, or alkaline phosphatase > 2.5 ×
upper limit of normal.
Doxorubicin Reduce dose by 50% if bilirubin 1.5–3.0 mg/dL.
Reduce dose by 75% if bilirubin 3.1–5.0 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Doxorubicin liposome Reduce dose by 50% if bilirubin 1.5–3.0 mg/dL.
Reduce dose by 75% if bilirubin 3.1–5.0 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Estramustine No dose reduction is necessary.
Etoposide Reduce dose by 50% if bilirubin 1.5–3.0 mg/dL
or SGOT 60–180 mg/dL.
Omit if bilirubin > 3 mg/dL or SGOT
> 180 mg/dL.
Etoposide phosphate Reduce dose by 50% if bilirubin 1.5–3.0 mg/dL
or SGOT 60–180 mg/dL.
Omit if bilirubin > 3 mg/dL or SGOT
> 180 mg/dL.
Floxuridine No dose reduction is necessary.
Fludarabine No dose reduction is necessary.
5-Fluorouracil Omit if bilirubin > 5.0 mg/dL.
Flutamide No formal recommendation for dose reduction.
Dose reduction may be necessary if bilirubin
> 3.0 mg/dL.
Gemcitabine No dose reduction is necessary.
Goserelin No dose reduction is necessary.
Hydroxyurea No dose reduction is necessary.
Idarubicin Reduce dose by 25% if bilirubin 1.5–3.0 mg/dL
or SGOT 60–180 mg/dL.
Reduce dose by 50% if bilirubin 3.0–5.0 or
SGOT > 180 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Ifosfamide No dose reduction is necessary.

380 Physicians’ Cancer Chemotherapy Drug Manual

Table 7. (cont)

Drug Recommended Dose Reduction for Hepatic Dysfunction

Imatinib Omit if bilirubin > 3 mg/dL or SGOT > 5 ×
ULN. Once bilirubin < 1.5 or SGOT < 2.5 ×
ULN, reduce dose from 400 mg to 300 mg or
from 600 mg to 400 mg.
Interferon-alpha No dose reduction is necessary.
Interleukin-2 Omit if signs of hepatic failure (ascites,
encephalopathy, jaundice) are observed. Do
NOT restart sooner than 7 weeks after recovery
from severe hepatic dysfunction.
Irinotecan No formal recommendation for dose reduction
in the presence of hepatic dysfunction. Dose
reduction may be necessary.
Isotretinoin No formal recommendation for dose reduction
in the presence of hepatic dysfunction. Dose
reduction may be necessary.
Leucovorin No dose reduction is necessary.
Leuprolide No dose reduction is necessary.
Lomustine No dose reduction is necessary.
Mechlorethamine No dose reduction is necessary.
Megestrol acetate No dose reduction is necessary.
Melphalan No dose reduction is necessary.
6-Mercaptopurine No dose reduction is necessary.
Mesna No dose reduction is necessary.
Methotrexate Reduce dose by 25% if bilirubin 3.1–5.0 mg/dL
or SGOT > 180 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Mitomycin-C No dose reduction is necessary.
Mitotane No formal recommendation for dose reduction
in the presence of hepatic dysfunction. Dose
reduction may be necessary.
Mitoxantrone Reduce dose by 25% if bilirubin > 3.0 mg/dL.
Nilutamide No formal recommendation for dose reduction.
Dose reduction may be necessary if bilirubin
> 3.0 mg/dL.
Oxaliplatin N/A

Guidelines for Chemotherapy and Dosing Modifications 381

 Table 7. (cont)

Drug Recommended Dose Reduction for Hepatic Dysfunction

Paclitaxel No formal recommendation for dose reduction
if bilirubin 1.5–3.0 mg/dL or SGOT
60–180 mg/dL.
Omit if bilirubin > 5.0 mg/dL or SGOT
> 180 mg/dL.
Pegasparaginase No dose reduction is necessary.
Pemetrexed No dose reduction is necessary.
Pentostatin No dose reduction is necessary.
Procarbazine No formal recommendation for dose reduction
in the presence of hepatic dysfunction. Dose
reduction may be necessary.
Rituximab No dose reduction is necessary.
Streptozocin No dose reduction is necessary.
Tamoxifen No dose reduction is necessary.
Temozolomide No dose reduction is necessary.
Thalidomide N/A
Thioguanine Omit if bilirubin > 5.0 mg/dL.
Thiotepa No formal recommendation for dose reduction
in the presence of hepatic dysfunction. Dose
reduction may be necessary.
Topotecan No dose reduction is necessary.
Trastuzumab N/A
Tretinoin Reduce dose to a maximum of 25 mg/m2 if
bilirubin 3.1–5.0 mg/dL or SGOT >
180 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
UFT No dose reduction is necessary.
Vinblastine No dose reduction if bilirubin < 1.5 mg/dL and
SGOT < 60 mg/dL.
Reduce by 50% if bilirubin 1.5–3.0 mg/dL and
SGOT 60–180 mg/dL.
Omit if bilirubin > 3.0 mg/dL or SGOT
> 180 mg/dL.
Vincristine No dose reduction if bilirubin < 1.5 mg/dL and
SGOT < 60 mg/dL.
Reduce by 50% if bilirubin 1.5–3.0 mg/dL and
SGOT 60–180 mg/dL.

382 Physicians’ Cancer Chemotherapy Drug Manual

Table 7. (cont)

Drug Recommended Dose Reduction for Hepatic Dysfunction

Omit if bilirubin > 3.0 mg/dL or SGOT
> 180 mg/dL.
Vinorelbine No dose reduction if bilirubin < 2.0 mg/dL.
Reduce dose by 50% if bilirubin 2.0–3.0 mg/dL.
Reduce dose by 75% if bilirubin 3.1–5.0 mg/dL.
Omit if bilirubin > 5.0 mg/dL.

N/A–not available
ULN–upper limit of normal

Table 8. General Guidelines for

Chemotherapy Dosage Based on
Renal Function
Drug Recommended Dose Reduction for Renal Dysfunction
Alemtuzumab N/A
Altretamine N/A
Amifostine N/A
Aminoglutethimide N/A
Amsacrine N/A
Anastrozole No dose reduction is necessary.
Arsenic trioxide No formal recommendation for dose reduction
in the presence of renal dysfunction. Dose
reduction may be necessary.
L-Asparaginase Omit if CrCl < 60 mL/min.
Bicalutamide No dose reduction is necessary.
Bleomycin No dose reduction if CrCl > 60 mL/min.
Reduce dose by 25% if CrCl 10–60 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
Buserelin N/A
Busulfan No dose reduction is necessary.
Capecitabine Reduce dose by 25% if CrCl 30–50 mL/min.
Omit if CrCl < 30 mL/min.
Carboplatin No dose reduction if CrCl > 60 mL/min.
AUC dose is modified according to CrCl.

Guidelines for Chemotherapy and Dosing Modifications 383

 Table 8. (cont)

Drug Recommended Dose Reduction for Renal Dysfunction

Carmustine Omit if CrCl < 60 mL/min.
Chlorambucil No dose reduction is necessary.
Cisplatin No dose reduction if CrCl > 60 mL/min.
Reduce dose by 50% if CrCl 30–60 mL/min.
Omit if CrCl < 30 mL/min.
Cladribine N/A
Cyclophosphamide No dose reduction if CrCl > 50 mL/min.
Reduce dose by 25% if CrCl 10–50 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
Cytarabine No formal recommendation for dose reduction
in the presence of renal dysfunction. Dose
reduction may be necessary.
Dacarbazine No formal recommendation for dose reduction
in the presence of renal dysfunction. Dose
reduction may be necessary.
Dactinomycin N/A
Daunorubicin Reduce dose by 50% if serum creatinine
> 3.0 mg/dL.
Dexrazoxane N/A
Docetaxel No dose reduction is necessary.
Doxorubicin No dose reduction is necessary.
Doxorubicin liposome No dose reduction is necessary.
Estramustine N/A
Etoposide No dose reduction if CrCl > 50 mL/min.
Reduce dose by 25% if CrCl 10–50 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
Etoposide phosphate No dose reduction if CrCl > 50 mL/min.
Reduce dose by 25% if CrCl 10–50 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
Floxuridine N/A
Fludarabine No formal recommendation for dose reduction
in the presence of renal dysfunction. Dose
reduction may be necessary.
5-Fluorouracil No dose reduction is necessary.
Flutamide N/A

384 Physicians’ Cancer Chemotherapy Drug Manual

Table 8. (cont)

Drug Recommended Dose Reduction for Renal Dysfunction

Gemcitabine No dose reduction is necessary.
Goserelin No dose reduction is necessary.
Hydroxyurea Reduce dose by 80% if CrCl < 10 mL/min.
Idarubicin No dose reduction is necessary.
Ifosfamide N/A
Imatinib No dose reduction is necessary.
Interferon-alpha No dose reduction is necessary.
Interleukin-2 Omit or discontinue if serum creatinine
> 4.5 mg/dL or serum creatinine > 4.0 mg/dL
in the presence of fluid overload.
Irinotecan No dose reduction is necessary.
Isotretinoin N/A
Leucovorin No dose reduction is necessary.
Leuprolide N/A
Lomustine Omit if CrCl < 60 mL/min.
Mechlorethamine N/A
Megestrol acetate N/A
Melphalan No dose reduction is necessary. However, use
with caution in the presence of renal
dysfunction.
6-Mercaptopurine No formal recommendation for dose reduction
in the presence of renal dysfunction. Adjust for
renal dysfunction by either increasing the
interval or decreasing the dose.
Mesna N/A
Methotrexate No dose reduction is necessary if CrCl
> 60 mL/min.
Reduce by 50% if CrCl 30–60 mL/min.
Omit if CrCl < 30 mL/min.
Mitomycin-C No dose reduction is necessary if CrCl
> 60 mL/min.
Reduce dose by 25% if CrCl 10–60 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
Mitotane N/A
Mitoxantrone No dose reduction is necessary.
Nilutamide No dose reduction is necessary.

Guidelines for Chemotherapy and Dosing Modifications 385

 Table 8. (cont)

Drug Recommended Dose Reduction for Renal Dysfunction

Oxaliplatin N/A
Paclitaxel No dose reduction is necessary.
Pegasparaginase N/A
Pemetrexed Dose reduction is necessary when CrCl
< 60 mL/min. and in proportion to the
reduction in CrCl.
Pentostatin No formal recommendation for dose reduction
in the presence of renal dysfunction. Dose
reduction may be necessary if CrCl
30–60 mL/min.
Procarbazine Omit if CrCl < 30 mL/min.
Rituximab N/A
Streptozocin Omit if CrCl < 60 mL/min.
Tamoxifen No dose reduction is necessary.
Temozolomide N/A
Thalidomide N/A
Thioguanine N/A
Thiotepa No formal recommendation for dose reduction
in the presence of renal dysfunction. Dose
reduction may be necessary.
Topotecan No dose reduction is necessary if CrCl
> 60 mL/min.
Reduce dose by 50% if CrCl 10–60 mL/min.
Omit if CrCl < 10 mL/min.
Trastuzumab N/A
Tretinoin Give a maximum of 25 mg/m2 in the presence
of renal dysfunction.
No dose reduction is necessary.
UFT No dose reduction is necessary.
Vinblastine
Vincristine No dose reduction is necessary.
Vinorelbine No dose reduction is necessary.
CrCl–creatinine clearance

N/A–not available

386 Physicians’ Cancer Chemotherapy Drug Manual

Table 9. Guidelines for Dialysis of
Chemotherapy Drugs
Hemodialysis Peritoneal Dialysis
Drug YES NO UNKNOWN YES NO UNKNOWN
Alemtuzumab X X
Altretamine X X
Aminoglutethimide X X
Amsacrine X X
Anastrozole X X
Arsenic trioxide X X
Bicalutamide X X
Bleomycin X X
Buserelin X X
Busulfan X X
Capecitabine X X
Carboplatin X X
Carmustine X X
Chlorambucil X X
Cisplatin X X
Cladribine X X
Cyclophosphamide X X
Cytarabine X X
Dacarbazine X X
Dactinomycin X X
Daunorubicin X X
Docetaxel X X
Doxorubicin X X
Doxorubicin liposome X X
Estramustine X X
Etoposide X X
Etoposide phosphate X X
Floxuridine X X
Fludarabine X X
5-Fluorouracil X X
Flutamide X X
Gemcitabine X X
Goserelin X X
Hydroxyurea X X
Idarubicin X X

Guidelines for Chemotherapy and Dosing Modifications 387

 Table 9. (cont)

Hemodialysis Peritoneal Dialysis

Drug YES NO UNKNOWN YES NO UNKNOWN
Ifosfamide X X
Imatinib X X
Irinotecan X X
Isotretinoin X X
Leuprolide X X
Lomustine X X
Mechlorethamine X X
Megestrol acetate X X
Melphalan X X
6-Mercaptopurine X X
Methotrexate X X
Mitomycin-C X X
Mitotane X X
Mitoxantrone X X
Nilutamide X X
Oxaliplatin X X
Paclitaxel X X
Pentostatin X X
Procarbazine X X
Rituximab X X
Streptozocin X X
Tamoxifen X X
Temozolomide X X
Thalidomide X X
Thioguanine X X
Thiotepa X X
Topotecan X X
Trastuzumab X X
Vinblastine X X
Vincristine X X
Vinorelbine X X

388 Physicians’ Cancer Chemotherapy Drug Manual

Table 10. Local Skin Toxicity Associated
with Administration of
Chemotherapy Drugs
Drug VESICANT IRRITANT
Aldesleukin No No
Amifostine No No
Amsacrine Yes No
L-Asparaginase No No
Bacillus Calmette-Guérin No No
Bleomycin No Yes
Busulfan No No
Carboplatin No Yes
Carmustine No Yes
Cisplatin No1 Yes
Cladribine No No
Cyclophosphamide No No
Cytarabine No No
Dacarbazine No Yes
Dactinomycin Yes No
Daunorubicin Yes No
Daunorubicin liposome No No
Denileukin diftitox No Yes
Dexrazoxane No Yes
Docetaxel No No
Doxorubicin Yes Yes
Doxorubicin liposome No Yes
Epirubicin Yes No
Etoposide No2 Yes
Floxuridine No No
Fludarabine No No
5-Fluorouracil No No
Gemcitabine No No
Idarubicin Yes No
Ifosfamide No Yes
Irinotecan No No
Mechlorethamine Yes No
Methotrexate No No
Mitomycin-C Yes No
Mitoxantrone Yes3 No

Guidelines for Chemotherapy and Dosing Modifications 389

 Table 10. (cont)

Drug VESICANT IRRITANT

Oxaliplatin No No
Paclitaxel Yes4 No
Pentostatin No No
Rituximab No No
Streptozocin Yes Yes
Thiotepa No Yes
Topotecan No No
Trastuzumab No No
Vinblastine Yes No
Vincristine Yes No
Vindesine Yes No
Vinorelbine Yes Yes

1 Cisplatin is vesicant if > 20 mL of 0.5 mg/mL solution extravasates.

2 Treatment is necessary only if a large volume of concentrated solution extravasates.
3 Ulceration rarely occurs unless concentrated doses infiltrate.
4 Weak vesicant.

Irritant
• Capable of inducing a local inflammatory reaction.

• Tenderness along the vein with burning and erythema.

• Intact blood return.

• Short-term injury that does not lead to tissue injury or necrosis.

Vesicant
• Infiltration of drug into surrounding tissue causes erythema and

blistering.
• Symptoms may be delayed for up to 6–12 hours after drug

extravasation. Complaints of pruritus are common in the absence of

pain.
• Severe necrosis with involvement of tendons and joints may occur.

• Absent blood return.

• Level of tissue damage depends on the vesicant potential of the drug,

the volume and concentration of drug infiltrated, the site of

infiltration, the length of drug exposure, and the immediate measures
taken once drug extravasation occurs.

390 Physicians’ Cancer Chemotherapy Drug Manual

Table 11. Classification of Teratogenic
Potential and Use-in-Pregnancy
for Chemotherapy Agents
Pregnancy Category A. Controlled studies show no risk in
pregnancy.
Controlled studies in pregnant women have not shown an increased risk
of fetal abnormalities when the drug is administered during pregnancy.
The possibility of fetal harm appears remote when the drug is used
during pregnancy.
Pregnancy Category B. No evidence of risk in pregnancy.
(a) Controlled studies in animals have shown that the drug poses a risk
to the fetus. However, studies in pregnant women have failed to show
such a risk.
(b) Controlled studies in animals do not show evidence of impaired
fertility or harm to the fetus. However, similar studies have not been
performed in humans. Because animal studies are not entirely predictive
of human response, the drug should be used during pregnancy only if
clearly needed.
Pregnancy Category C. Risk in pregnancy cannot be ruled out.
Controlled studies either have not been conducted in animals or show
that the drug is teratogenic or has an embryocidal effect and/or other
adverse effect in animals. However, there are no adequate and well-
controlled studies in pregnant women. The drug should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus.
Pregnancy Category D. Clear evidence of risk in pregnancy.
The drug can cause fetal harm when administered to a pregnant
woman. If the drug is used during pregnancy, or if a patient becomes
pregnant while taking this drug, the patient should be informed of the
potential hazard to the fetus. However, the potential benefits of
treatment may outweigh any potential risk.
Pregnancy Category X. Absolutely contraindicated in pregnancy.
The drug has been shown to cause fetal harm when administered to a
pregnant woman. The drug is absolutely contraindicated in women who
are or may become pregnant. If this drug is used during pregnancy, or
if a patient becomes pregnant while taking this drug, the patient should
be informed of the potential hazard to the fetus. The potential risk, in
this case, outweighs any potential benefit from treatment.

Guidelines for Chemotherapy and Dosing Modifications 391