Medication Summary
Chemotherapy regimens for testicular cancers are divided into initial and salvage chemotherapy, according to tumor stage, status, and risk stratification.
Initial Chemotherapy Regimens
Carboplatin (for stage I seminoma)
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Carboplatin area under the curve (AUC) 7 (see Carboplatin AUC Dose Calculation [Calvert Formula]) for one or two cycles
BEP (5-day schedule)
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Bleomycin 30 U or 30 mg IV bolus day 1, 8, 15 or day 2, 9, 16
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Etoposide (VP-16) 100 mg/m 2/day IV for 5 days
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Cisplatin (CDDP) 20 mg/m 2/day IV for 5 days
This regimen is administered for three to four cycles at 21-day intervals
EP
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Etoposide (VP-16) 100 mg/m 2/day IV daily for 5 days
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Cisplatin (CDDP) 20 mg/m 2/day IV daily for 5 days
This regimen is administered for four cycles at 21-day intervals
VIP (for patients with underlying lung disease)
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Etoposide (VP-16) 75 mg/m 2/day IV daily for 5 days
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Ifosfamide 1.2 g/m 2/day IV daily for 5 days
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Cisplatin (CDDP) 20 mg/m 2/day IV for days 1-5
Mesna 120 mg/m2 slow IV bolus is given before ifosfamide day 1, followed by 1200 mg/m2/day continuous infusion on days 1-5.
This regimen is administered for four cycles at 21-day intervals
Salvage Chemotherapy Regimens
VeIP (for patients who received prior etoposide)
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Vinblastine 0.11 mg/kg/ IV daily for 2 days
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Ifosfamide 1,200 mg/m 2 IV daily for 5 days
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Mesna 400 mg/m 2 IV every 8 hours for 5 days
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Cisplatin (CDDP) 20 mg/m 2 IV daily for 5 days
This regimen is administered for four cycles at 21-day intervals.
TIP
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Paclitaxel 250 mg/m2 IV day 1 followed by ifosfamide 1500 mg/m 2 IV daily days 2-5 and cisplatin (CDDP) 25 mg/m 2 IV daily on days 2-5
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Mesna 500 mg/m 2 IV before ifosfamide, and then 4 and 8 hrs after each dose of ifosfamide daily on days 2-5
This regimen is administered for four cycles at 21-day intervals.
GEMOX (palliative second-line)
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Gemcitabine 1000 or 1250 mg/m 2 IV on days 1 and 8, plus oxaliplatin 130 mg/m 2 IV on day 1, administered every 3 weeks
Antineoplastic Agent, Topoisomerase II Inhibitors
Class Summary
These agents may cause DNA strand breaks, which may result in the inhibition of cell growth and proliferation.
Etoposide (Toposar)
Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single- and double-strand DNA breaks. This causes cell proliferation to arrest in late S or early G2 portion of the cell cycle.
Therapy should be withheld or suspended if platelet counts are < 50,000 or absolute neutrophil counts are < 500/mm3. Reduce dose 20% for granulocytic fever or previous radiotherapy. Reduce dose in hepatic (increased total bilirubin [TB]) and renal (decreased CrCl) impairment.
Antineoplastic Agent, Antibiotics
Class Summary
Agents in this class may cause single and double DNA strand breaks and may inhibit RNA and protein synthesis.
Bleomycin
Group of glycopeptides extracted from Streptomyces species. Each molecule has a planar end and an amine end; different glycopeptides of the group differ in their terminal amine moieties. Planar end intercalates with DNA, while amine end facilitates oxidation of bound ferrous ions to ferric ions, thereby generating free radicals, which subsequently cleave DNA, acting specifically at purine-G-C-pyrimidine sequences.
Not absorbed when given orally; peak levels reached in about 30-60 min when given IM and are only one third of levels obtained after IV administration; approximately 50% of drug absorbed systemically after intrapleural or intraperitoneal administration; systemic absorption after intracavitary administration for craniopharyngioma not negligible.
Volume of distribution is 20-30 L both in intracellular and extracellular fluid.
Less than 10% is bound to plasma proteins.
Bleomycin has plasma half-life of less than 1 h and terminal half-life of 2-4 h, but it could be as long as 22 h in patients with renal dysfunction or those previously treated with cisplatin.
About 50% eliminated in urine within 24 h. Most tissues (known exceptions—skin and lungs) contain an enzyme, bleomycin hydrolase (most active tissues are liver and kidney), which readily inactivates drug; therefore, toxicity is tissue specific, occurring in tissues lacking this enzyme. Bleomycin mostly used systemically in combination with other drugs (mostly with cisplatin and vincristine).
Principal mechanisms of resistance include high levels of bleomycin hydrolase, cell mutations altering DNA sequences to prevent intercalation, poor cell accumulation of drug, and rapid plasma removal. None of these factors plays important role when bleomycin administered locally in residual cyst.
Toxicity is age dependent and cumulative dose related; systemic administration mostly causes pulmonary toxicity. This consists of pneumonitis, which can progress to fatal pulmonary fibrosis.
Maximum recommended total cumulative dose for systemic use is 400 U. Unit measurement based on toxicity to bacteria; 1 U equals approximately 1.7 mg.
Administered systemically, does not produce significant bone marrow toxicity. Toxicity with local administration due to both systemic contamination (when anaphylactoid reactions, transient fever, nausea, and vomiting could occur) and leakage into surrounding neural tissue. Fatal outcome has been reported with leakage, due to subsequent diffuse diencephalon and brainstem edema.
Contrast CT cystography is required prior to intracavitary administration to ensure cyst wall integrity; when inconclusive, MR cystography with gadopentetate dimeglumine has been advocated.
Antineoplastic Agent, Alkylating Agents
Class Summary
These agents may inhibit DNA synthesis and disrupt DNA function.
Cisplatin
Platinum-containing compound that exerts antineoplastic effect by covalently binding to DNA with preferential binding to N-7 position of guanine and adenosine. Can react with 2 different sites on DNA to cause cross-links. Platinum complex also can bind to nucleus and cytoplasmic protein. A bifunctional alkylating agent, once activated to aquated form in cell, binds to DNA, resulting in interstrand and intrastrand cross-linking and denaturation of double helix.
Modify dose on basis of CrCl. Avoid use if CrCl < 60 mL/min.
Ifosfamide (Ifex)
Alkylating agent activated in liver to phosphoramide mustard and acrolein. Phosphoramide mustard cross-links DNA strands and is responsible for therapeutic effect. Acrolein related to bladder toxicity.
Oxaliplatin (Eloxatin)
Platinum-based antineoplastic agent forms interstrand and intrastrand Pt-DNA crosslinks that inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific.
Carboplatin
Analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication. Binds to protein and other compounds containing SH group. Cytotoxicity can occur at any stage of the cell cycle, but cell is most vulnerable to action of these drugs in G1 and S phase.
Has same efficacy as cisplatin but with better toxicity profile. Main advantages over cisplatin include less nephrotoxicity and ototoxicity not requiring extensive prehydration, less likely to induce nausea and vomiting, but more likely to induce myelotoxicity.
Dose is based on the following formula: total dose (mg) = (target AUC) x (GFR+25) where AUC (area under plasma concentration-time curve) is expressed in mg/mL/min and GFR (glomerular filtration rate) is expressed in mL/min.
Antineoplastic Agents, Antimicrotubular
Class Summary
Agents in this class may distort mitotic spindles and result in breakage of chromosomes.
Paclitaxel
Mechanisms of action are tubulin polymerization and microtubule stabilization.
Antineoplastic Agent, Vinca Alkaloids
Class Summary
These agents may inhibit microtubule formation.
Vinblastine
Vinca alkaloid, inhibits microtubule formation, which disrupts formation of mitotic spindle, causing cell proliferation to arrest at metaphase.
Antineoplastic Agent, Antimetabolites
Class Summary
Agents in this class are pyrimidine antimetabolites that inhibit DNA synthesis.
Gemcitabine (Gemzar)
Cytidine analog, after intracellular metabolism to active nucleotide, inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Cell-cycle specific for S phase.
This drug has been shown to have activity in a phase 2 trial against relapsed germ cell tumors.
Antidote, Cyclosphosphamide-induced Hemorrhagic Cystitis
Class Summary
Agents in this class may inactivate acrolein, the urotoxic metabolite from ifosfamide and cyclophosphamide.
Mesna (Mesnex)
Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
Tables
Race/Ethnicity |
Annual rate per 100,000 men |
All Races |
6.0 |
White |
7.4 |
Black |
1.7 |
Asian/Pacific Islander |
2.3 |
American Indian/Alaska Native |
7.4 |
Hispanic |
5.9 |
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Stage |
LDH |
HCG (mIU/mL) |
AFP (ng/mL) |
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S1 |
< 1.5 times normal |
< 5,000 |
< 1,000 |
S2 |
1.5-10 times normal |
5,000-50,000 |
1,000-10,000 |
S3 |
>10 times normal |
>50,000 |
>10,000 |
LDH=lactate dehydrogenase; HCG=beta human chorionic gonadotropin; AFP=alpha fetoprotein. |
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- Overview
- Presentation
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- Workup
- Treatment
- Guidelines
- Medication
- Medication Summary
- Antineoplastic Agent, Topoisomerase II Inhibitors
- Antineoplastic Agent, Antibiotics
- Antineoplastic Agent, Alkylating Agents
- Antineoplastic Agents, Antimicrotubular
- Antineoplastic Agent, Vinca Alkaloids
- Antineoplastic Agent, Antimetabolites
- Antidote, Cyclosphosphamide-induced Hemorrhagic Cystitis
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