VA Class:AN100
Thiotepa is an alkylating antineoplastic agent that is chemically related to nitrogen mustard.
Thiotepa has been used intravesically for the treatment of residual tumor and/or as adjuvant therapy for prophylaxis of superficial bladder cancer.103, 104, 105, 106, 111 In small studies in patients with papillary bladder tumors, complete response rates of approximately 30-35% have been reported with the use of intravesical thiotepa.104, 105 Intravesical thiotepa is less effective than intravesical BCG live in reducing the frequency of tumor recurrence in patients with superficial bladder cancer.107 In a randomized trial, a single instillation of thiotepa immediately following completion of transurethral resection (TUR) did not reduce the tumor recurrence rate compared with TUR alone.108 Compared with other cytotoxic agents used for intravesical therapy, large amounts of the dose may be systemically absorbed when thiotepa is administered intravesically resulting in increased incidence of systemic toxicity, particularly myelosuppression.109 Because of the limited efficacy and high incidence of systemic toxicity associated with intravesical thiotepa, some clinicians prefer other agents (e.g., mitomycin) for the intravesical chemotherapy of superficial bladder cancer.104, 106, 110, 111, 112 Other clinicians state that intravesical thiotepa may be used with caution as long as peripheral blood cell counts are monitored carefully.113, 114 (See Uses: Bladder Cancer in Mitomycin 10:00 for further discussion of intravesical chemotherapy for superficial bladder cancer.)
Thiotepa is labeled for use in the treatment of adenocarcinoma of the breast or ovary,100 but other agents are preferred for the treatment of these neoplasms.111
Thiotepa may be used by intracavitary injection to control pleural, pericardial, or peritoneal effusions caused by metastatic tumors.100 Although sclerosing agents are often used to control malignant effusions, thiotepa may be preferred in some patients because of its antitumor effect.
Thiotepa has been used as an ophthalmic instillation† to prevent the recurrence of pterygium following surgical excision; however, postoperative β-irradiation is generally preferred as preventive therapy because it results in a low incidence of recurrence and is relatively easy to administer. Many clinicians recommend that the use of thiotepa be limited to the management of pterygium which recurs following postoperative β-irradiation.
Intrathecal† thiotepa has been investigated to a limited extent in the treatment of malignant meningeal neoplasms (e.g., leukemia), but additional studies are required to determine its efficacy and safety.
Reconstitution and Administration
Thiotepa may be administered by IV, intrapleural, intraperitoneal, intrapericardial, or intratumor injection, or by intravesical instillation. The drug has also been administered IM†, intrathecally†, and as an ophthalmic instillation†.
The manufacturer recommends that protective gloves be used during handling of commercially available thiotepa injection since skin reactions associated with accidental exposure to the drug may occur.100 If thiotepa solution comes in contact with the skin or mucosa, the affected skin should be washed immediately and thoroughly with soap and water and the affected mucosa should be rinsed thoroughly with water.100
Thiotepa for injection is usually reconstituted with sterile water for injection, as other diluents produce hypertonic solutions which may cause mild to moderate discomfort on injection. The powder for injection should be reconstituted by adding 1.5 mL of sterile water for injection to a vial labeled as containing approximately 15 mg of the drug or 3 mL of sterile water for injection to a vial labeled as containing approximately 30 mg of the drug.100 The resultant solution contains about 10 mg of thiotepa per mL and may be administered rapidly IV. Since reconstituted solutions of thiotepa are hypotonic, they must be further diluted with 0.9% sodium chloride injection immediately before use.100 In order to eliminate haze, these reconstituted solutions of the drug should be filtered with a pore size of 0.22 µm (e.g., polysulfone membrane [Gelman Sterile Acrodisc®, single use], triton-free mixed ester of cellulose/PVC [Millipore Millex®-GS Filter Unit]).100, 102 Reconstituted solutions of the drug that are opaque or contain a precipitate after filtration should not be used.100, 102 Parenteral thiotepa solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.100 If larger volumes of solution are desired for intracavitary, IV infusion, or perfusion therapy, the reconstituted solution may be diluted with sodium chloride, dextrose, dextrose and sodium chloride, Ringer's, or lactated Ringer's injection. For local administration, thiotepa may be mixed with 2% procaine hydrochloride injection and/or 0.1% (1:1000) epinephrine hydrochloride injection.
Dosage of thiotepa must be based on the clinical and hematologic response and tolerance of the patient in order to obtain optimum therapeutic results with minimum adverse effects. Slow response to thiotepa does not necessarily indicate lack of effect and increasing the dosage may only increase drug-associated toxicity.100 The delayed myelosuppressive effects of the drug must be considered. (See Cautions: Hematologic Effects.) Initially, the higher dose in a given dosage range is administered. Maintenance doses should be adjusted on the basis of pretreatment and subsequent blood counts and should not be administered at intervals of less than 1 week.
Thiotepa may be given rapidly IV in doses of 0.3-0.4 mg/kg at intervals of 1-4 weeks.100 The drug has also been given IV in doses of 0.2 mg/kg or 6 mg/m2 daily for 4 or 5 days at intervals of 2-4 weeks. Thiotepa has also been given IM† in doses of 15-30 mg in various schedules.
The usual intracavitary dose of thiotepa is 0.6-0.8 mg/kg100 at intervals of at least one week, although a dose of 15-30 mg has been used intrapericardially. The drug is generally administered through the same tubing used to drain effusion fluid from the involved cavity.100 Specialized references should be consulted for specific techniques of administration.
For intratumor injection, initial doses of 0.6-0.8 mg/kg may be administered directly into the tumor via a 22-gauge needle. A small amount of local anesthetic is usually injected first, and the needle left in place; a separate syringe containing the calculated dose of thiotepa is then used to inject the drug through the same needle. Maintenance doses of 0.07-0.8 mg/kg are administered into the tumor at 1- to 4-week intervals.
For intravesical instillation in the treatment of superficial bladder tumors, the dose of thiotepa generally ranges from 30-60 mg. The manufacturer recommends 60 mg of thiotepa in 30-60 mL of 0.9% sodium chloride injection be instilled by catheter into the bladder of the patient who has been dehydrated for 8-12 hours.100 For maximum effect, the solution should be retained in the bladder for 2 hours.100 The patient may be repositioned every 15 minutes for maximum area contact.100 If the patient is unable to retain 60 mL for 2 hours, the dose may be given in 30 mL. The usual course of treatment is once a week for 4 weeks.100 The course of treatment may be repeated if necessary, but additional courses should be given with caution because of the cumulative myelosuppressive properties of thiotepa (see Cautions: Hematologic Effects), and some clinicians recommend reduced doses of the drug for additional courses. Following a course of treatment, most clinicians instill thiotepa once monthly. For prophylaxis following local resection and/or fulguration of bladder tumors, 30-60 mg of thiotepa has usually been instilled intravesically once a week for 4 weeks and then once monthly, beginning 1-3 weeks after surgery; however, many clinicians currently initiate therapy sooner after surgery (e.g., within 48 hours). Various regimens have been used and clinicians should consult published protocols for the dosage and schedule of administration and duration of therapy. Some clinicians suggest that therapy can probably be discontinued after 1 year of monthly instillations if the patient remains free of tumor. The intravesical dose of thiotepa may need to be reduced in elderly patients or in patients with extensive local resection and/or fulguration of bladder tumors.
In the treatment of malignant meningeal neoplasms, intrathecal† thiotepa doses of 1-10 mg/m2 have been administered once or twice weekly in concentrations of 1 mg/mL diluted with sterile water for injection.
To prevent pterygium recurrence, a 0.05% solution of thiotepa in Ringer's injection has been instilled into the eye(s)† every 3 hours during waking hours for 6-8 weeks postoperatively.
The major adverse effect of thiotepa is hematologic toxicity, which is usually dose related and cumulative. Adverse hematopoietic effects include leukopenia, anemia, thrombocytopenia, and pancytopenia which is sometimes fatal. Hematologic status must be carefully monitored in patients receiving thiotepa. (See Cautions: Precautions and Contraindications.) Although the leukocyte nadir may occur at 10-14 days when thiotepa is given once weekly IV, initial effects on bone marrow may not be evident for up to 30 days. Because of absorption through serous membranes, intracavitary and intravesical instillation of thiotepa can produce systemic adverse effects of varying severity, and deaths resulting from bone marrow depression secondary to systemic absorption of the drug, have occurred following intravesical instillation of the drug.
Nausea, vomiting, abdominal pain, and anorexia occur infrequently after administration of thiotepa. Stomatitis and ulceration of the intestinal mucosa also have been reported.100
Dermatologic and Sensitivity Reactions
Hypersensitivity reactions, including allergic reactions, rash, urticaria, laryngeal edema, asthma, anaphylactic shock, and wheezing have occurred in patients receiving thiotepa. Contact dermatitis and alopecia also have been reported. Skin depigmentation has been reported following topical use of the drug.100
Other reported adverse effects of thiotepa include pain at the injection site, headache, dizziness, blurred vision, conjunctivitis, dysuria, urinary retention, amenorrhea, and tightness of the throat. Some symptoms such as hyperuricemia or febrile reactions and exudation from subcutaneous lesions may be due to breakdown of tumor tissue. In some patients, intravesical administration of thiotepa has been reported to produce lower abdominal pain, vesical irritability, hematuria, and rarely hemorrhagic chemical cystitis.
Ophthalmic instillation† of thiotepa may occasionally produce irritation or periorbital skin depigmentation; the depigmentation usually occurs 6 months or longer after cessation of treatment. Intrathecal† administration of thiotepa has been associated with lower extremity weakness and pain and demyelination within the spinal cord in some patients; transient paresthesia of the lower extremities also has occurred following intrathecal administration of hypertonic solutions of the drug.
Precautions and Contraindications
Thiotepa is a highly toxic drug with a low therapeutic index, and a therapeutic response is not likely to occur without some evidence of toxicity. The drug must be used only under constant supervision by clinicians experienced in therapy with cytotoxic agents.
Patients who receive myelosuppressive drugs experience an increased frequency of infections (even septicemia) as well as possible hemorrhagic complications. Because these complications are potentially fatal, the patient should be instructed to notify the clinician if fever, chills, sore throat, discoloration of urine, black stools, or unusual bleeding (e.g., epistaxis) or easy bruising occurs. The patient's hematologic status must be carefully monitored and blood counts performed at least weekly during therapy and for at least 3 weeks after thiotepa has been discontinued. Therapy should be discontinued temporarily or dosage decreased if the leukocyte or platelet count declines rapidly. The manufacturer further suggests that thiotepa therapy should be discontinued if the leukocyte count falls to 3000/mm3 or less, or if the platelet count falls below 150,000 per mm3. Treatment of severe hematologic toxicity may consist of supportive therapy, antibiotics for complicating infections, and blood product transfusions. The manufacturer recommends that thiotepa not be administered sequentially with other alkylating agents or radiation therapy until the patient recovers from previously induced myelosuppression as indicated by the leukocyte count, and particular caution should be exercised in administering other myelosuppressive agents to patients receiving thiotepa.
Thiotepa may inhibit pseudocholinesterase activity and succinylcholine should be administered with caution to patients receiving thiotepa. One patient who had received thiotepa and other antineoplastic agents reportedly experienced prolonged apnea after administration of succinylcholine prior to surgery.
Thiotepa is contraindicated in patients with a history of hypersensitivity to the drug. The manufacturer states that thiotepa is probably also contraindicated in patients with preexisting hepatic, renal, or bone marrow dama if therapy is necessary in these patients, thiotepa should be administered in low doses and hepatic, renal, and hematopoietic function should be carefully monitored.
The manufacturer states that safety and efficacy of thiotepa in children have not been established.100
Safety and efficacy of thiotepa in geriatric patients have not been studied specifically to date.100 Clinical studies of thiotepa did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.115 While other clinical experience has not revealed age-related differences in response or tolerance, drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range.115 The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.115
Mutagenicity and Carcinogenicity
Since thiotepa is a polyfunctional alkylating agent capable of cross-linking DNA within a cell, changing its nature and thus altering replication of a cell, the drug is considered mutagenic.100 One in vitro study has shown that thiotepa causes chromosomal aberrations of the chromatid type; the frequency of such aberrations increases with age of the patient.100 In addition, the drug was mutagenic in various in vitro microbial tests using Salmonella typhimurium and Escherichia coli and the Chinese hamster lung and lymphocyte tests.100 Chromosomal aberrations and sister chromatid exchanges were observed in vitro with thiotepa in bean root tips, human lymphocytes, Chinese hamster lungs, and monkey lymphocytes.100 Mutations also were observed in mice receiving oral administration of thiotepa at doses exceeding 2.5 mg/kg (8 mg/m2).100 Positive results also were reported in the mouse micronucleus test following intraperitoneal administration of thiotepa at doses exceeding 1 mg/kg (3.2 mg/m2).100 In addition, thiotepa was mutagenic in several in vivo chromosomal aberration or mutation assays including Drosophila melanogaster , Chinese hamster marrow, murine marrow, monkey lymphocyte, and murine germ cell.100
Thiotepa, like other alkylating agents, has been reported to be carcinogenic in animals (e.g., mice); however, limited data also indicate that the drug may be carcinogenic in humans.100 Although a causal relationship has not been definitely established, the possibility of development of a secondary malignancy should be considered in patients receiving thiotepa.
In mice, repeated intraperitoneal administration of thiotepa at dosages 1.15 or 2.3 mg/kg 3 times a week for 52 or 43 weeks, respectively, was associated with substantial increases in the combined incidence of squamous cell carcinomas of the skin, preputial gland, and ear canal, and also in the combined incidence of lymphoma and lymphocytic leukemia.100 In addition, repeated intraperitoneal administration of thiotepa in mice receiving dosages of 4 or 8 mg/kg given 3 times a week for 4 weeks followed by a 20-week observation period or thiotepa dosages of 1.8 mg/kg given 3 times a week for 4 weeks followed by a 35-week observation period resulted in increased incidence of lung tumors.100 In rats, repeated intraperitoneal administration of thiotepa receiving dosages of 0.7 or 1.4 mg/kg given 3 times a week for 52 or 34 weeks, respectively, resulted in substantial increases in the incidence of squamous cell carcinoma of the skin or ear canal, combined hematopoietic neoplasms, and uterine adenocarcinomas.100 In rats, IV administration of thiotepa (1 mg/kg given once a week for 52 weeks) was associated with an increased incidence of malignant tumors (e.g., abdominal cavity sarcoma, lymphosarcoma, myelosis, seminoma, fibrosarcoma, salivary gland hemangioendothelioma, mammary sarcoma, pheochromocytoma) and benign tumors.100 In mice or rats, the lowest reported carcinogenic dose is 1.15 mg/kg (3.68 mg/m2; sevenfold less than the maximum recommended therapeutic dose in humans based on body surface area) or 0.7 mg/kg (4.9 mg/m2; sixfold lower than the maximum recommended therapeutic dose in humans based on body surface area), respectively.100
Thiotepa can cause fetal harm when administered to pregnant women. In mice, intraperitoneal administration of thiotepa at doses exceeding or equal to 1 mg/kg (3.2 mg/m2; eightfold lower than the maximum recommended therapeutic dose in humans based on body surface area) were associated with teratogenicity.100 Teratogenicity also was reported in rats receiving intraperitoneal administration of thiotepa at doses exceeding or equal to 3 mg/kg (21 mg/m2; approximately equal to the maximum recommended therapeutic dose in humans based on body surface area).100 Lethality was observed in rabbits receiving thiotepa at doses of 3 mg/kg (41 mg/m2; approximately twice the maximum recommended therapeutic dose in humans based on body surface area).100 The manufacturer recommends that an effective method of contraception be used during therapy with the drug if either the patient or the sexual partner is of childbearing potential.100 There are no adequate and controlled studies to date using thiotepa in pregnant women.100 When the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient and sexual partner should be informed of the potential hazard to the fetus.100 Women of childbearing potential should be advised to avoid becoming pregnant during thiotepa therapy.100
Impairment of fertility has been reported in male mice receiving oral or intraperitoneal thiotepa at dosages exceeding or equal to 0.7 mg/kg (2.24 mg/m2; approximately 12-fold lower than the maximum recommended therapeutic dose in humans based on body surface area).100 Inhibition of implantation was observed in rats following instillation of 0.5 mg doses of thiotepa into the uterine cavity.100 Impaired spermatogenesis was reported in mice or hamsters receiving intraperitoneal thiotepa at dosages exceeding or equal to 0.5 mg/kg (1.6 mg/m2; approximately 17-fold lower than the maximum recommended therapeutic dose in humans based on body surface area) or 1 mg/kg (4.1 mg/m2; approximately sevenfold lower than the maximum recommended therapeutic dose in humans based on body surface area), respectively.100
Impaired spermatogenesis has occurred in patients receiving thiotepa.
It is not known whether thiotepa is excreted in human milk.100 Because many drugs are excreted in human milk and because of the potential for tumorigenicity of thiotepa if it were distributed, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.100
Overdosage with thiotepa would be expected to produce effects that are mainly extensions of common adverse reactions, particularly leukopenia and thrombocytopenia, effects that may lead to infection and/or bleeding.100 Anemia is a less accurate indicator of thiotepa-associated toxicity.100 Thiotepa dosages within or minimally above the recommended therapeutic dosages have been associated with dose-related, life-threatening hematopoietic toxicity.100 There is no known antidote for thiotepa overdosa whole blood or platelet transfusions have been beneficial in patients with hematopoietic toxicity.100 Thiotepa is removed by dialysis.100
Thiotepa, as an alkylating agent, interferes with DNA replication and transcription of RNA, and ultimately results in the disruption of nucleic acid function. Thiotepa also possesses some immunosuppressive activity.
Following intracavitary administration, thiotepa may control malignant effusions by a direct antineoplastic effect.
Absorption of thiotepa from the GI tract is variable, since the drug is unstable in the acidic pH of the stomach.102 Variable absorption also occurs through serous membranes, such as the pleura and bladder, and from IM injection sites. Absorption through the bladder mucosa may range from 10% to almost 100% of the instilled dose and is enhanced by extensive tumor infiltration or acute mucosal inflammation, following endoscopic surgical procedures or radiation therapy, and in the presence of vesicoureteral reflux.
Following IV administration of thiotepa, peak plasma concentrations of the drug occur immediately and are proportional to the dose administered.102 Following IV administration of 60 or 80 mg of thiotepa in women with advanced ovarian carcinoma, mean peak serum concentrations of thiotepa were 1.3 or 1.8 mcg/mL, respectively, while mean peak serum concentrations of TEPA the main metabolite of the drug were about 0.27 or 0.35 mcg/mL, respectively.100, 102 Following IV administration of thiotepa C 14, serum concentrations of radioactivity reportedly begin to decline within 10 minutes, but detectable concentrations persist 72 hours. Following intravesical administration of 30 mg of thiotepa, plasma concentrations of thiotepa are detected within 15 minutes, peak plasma concentrations of 0.1 mcg/mL occur within 1 hour, and plasma concentrations of the drug decline rapidly thereafter; plasma concentrations of the main metabolite TEPA are detected within 15 minutes and remain relatively constant for at least 6 hours, with mean plasma concentrations of 30 ng/mL exceeding those of the parent drug.102 Following intraperitoneal administration of 30- to 80-mg/m2 doses of thiotepa, approximately 80-100% of the dose was absorbed into systemic circulation; peak intraperitoneal concentrations, which occurred immediately after administration, were about 4-22 mcg/mL.102
Distribution of thiotepa and TEPA, the drug's main metabolite, into human body tissues has not been fully elucidated.102 Following IV administration of thiotepa in mice, the drug is rapidly and extensively distributed into brain, heart, lung, kidney, and skeletal muscle.102 Thiotepa and TEPA distribute readily into CSF following IV administration with CSF concentrations of the parent drug approximately equivalent to those in plasma; CSF concentrations of TEPA are equivalent to those in plasma 3-5 hours after IV administration of thiotepa.102 Following IV administration of thiotepa in adults, the volume of distribution of thiotepa is 0.25-0.32-0.19 L/kg in the central compartment; the apparent volume of distribution (V) of the drug has been reported to be 50 L (about 0.7-0.8 L/kg) while the volume of distribution at steady state (Vss) has been reported to be approximately 0.7-1.6 L/kg.102 In vitro, at concentrations 1 mcg/mL, thiotepa is approximately 8-13% bound to serum proteins, mainly to albumin and to lipoproteins; at lower concentrations (0.1 mcg/mL) the drug is reportedly 29% bound to albumin and, to a lesser extent to globulins, while TEPA is more extensively bound to albumin and α-globulins.102
It is not known if thiotepa or its metabolites are distributed into milk.
Thiotepa appears to be extensively metabolized in the liver by the cytochrome P-450 microsomal enzyme system, principally via oxidative desulfuration to a triethylenephosphoramide (TEPA).102 Although TEPA is the only metabolite detected and identified in plasma, there is evidence that other unidentified metabolites also are formed.102 Following rapid IV injection of thiotepa in adults with normal renal and hepatic function, plasma concentrations of the drug appear to decline in a biphasic manner with a half-life of approximately 6-12 minutes in the initial phase and 1.2-2.9 hours in the terminal phase.102 The plasma elimination half-life of TEPA is about 10-21 hours.102 Following rapid IV injection of thiotepa in adults, total body clearance is about 180-780 mL/minute per m2and renal clearance of the drug is less than 1% of the total body clearance.102 The effects of renal and/or hepatic impairment on the pharmacokinetics of thiotepa have not been fully evaluated; however, very limited data indicate that clearance of the drug may be decreased in patients with hepatic impairment.102
In patients with normal renal function, thiotepa, TEPA, and unidentified metabolites with alkylating activity are excreted in urine.102 Urinary excretion of thiotepa, TEPA, and unidentified metabolites with alkylating activity is about 0.1-1.5, 4, and 13-24% of the dose, respectively, within the first 24-48 hours;102 urinary excretion of the parent drug is complete within the first 6-8 hours.102 Fecal excretion of the drug and its metabolites has not been studied.102 Following IV administration of high doses of thiotepa, the drug apparently is excreted in sweat to an appreciable extent.102
Thiotepa, an ethylenimine derivative, is a polyfunctional alkylating agent that is chemically related to nitrogen mustard. The drug occurs as fine, white, crystalline flakes having a faint odor. Thiotepa is soluble in water and freely soluble in alcohol, having solubilities of approximately 76.9 and 120.5 mg/mL, respectively, at 25°C.102 Thiotepa for injection is a sterile, nonpyrogenic, lyophilized powder; following reconstitution of thiotepa with sterile water for injection to a concentration of about 10 mg/mL, the solution is hypotonic, may be clear to slightly opaque, and has a pH of 5.5-8.1.100, 102, 115
Both thiotepa powder for injection and reconstituted solutions of the drug should be stored at 2-8°C protected from light. Although there are no studies evaluating the stability of thiotepa powder for injection at temperatures exceeding 8°C, the manufacturer states that at higher temperatures thiotepa is inactivated by polymerization which occurs faster in warm and moist conditions.102
Reconstituted thiotepa solutions containing 10 mg/mL in sterile water for injection should be stored at 2-8°C and should be used within 8 hours.102 Reconstituted solutions should be further diluted with 0.9% sodium chloride injection.100, 101, 102 These further diluted thiotepa solutions containing approximately 1-3 mg/mL in 0.9% sodium chloride injection are stable for 24 hours at 25°C or 48 hours at 8°C;101 solutions containing 5 mg/mL are stable for 24 hours when stored at 23°C or under refrigeration (8°C).101 In order to eliminate haze, these reconstituted solutions of the drug should be filtered with a pore size of 0.22 µm (e.g., polysulfone membrane [Gelman Sterile Acrodisc®, single use], triton-free mixed ester of cellulose/PVC [Millipore Millex®-GS Filter Unit]).100, 102 Reconstituted solutions of the drug that are opaque or contain a precipitate after filtration should not be used.100, 102 Thiotepa is unstable in acidic aqueous solutions and undergoes degradation to 2-chloroethyl moieties (by successive openings of the aziridine ring); the drug is stable in alkaline aqueous solutions.100, 102
Additional Information
For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection | 15 mg* | Thiotepa for Injection | |
30 mg* | Thiotepa for Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
100. Gensia Sicor Pharmaceuticals, Inc. Thiotepa for injection prescribing information. Irvine, CA; 2000 Dec.
101. Immunex, Seattle, WA: Personal communication.
102. Immunex. Thiotepa for injection technical monograph. Seattle, WA; 1995 Jul.
103. Bladder cancer. From: CancerNet/PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2001 Oct.
104. Witjes JA. Current recommendations for the management of bladder cancer: drug therapy. Drugs . 1997; 53:404-14. [PubMed 9074842]
105. Bouffioux C, van der Meijden A, Kurth KH et al. Objective response of superficial bladder tumors to intravesical treatment (including review of response of marker lesions). Prog Clin Biol Res . 1992; 378:29-42. [PubMed 1301584]
106. Schulman CC, Robinson M, Denis L et al. Prophylactic chemotherapy of superficial transitional cell bladder carcinoma: an EORTC randomized trial comparing thiotepa, an epipodophyllotoxin (VM26) and TUR alone. Eur Urol . 1982; 8:207-12. [PubMed 6807679]
107. Novak R, Kern J, Fister H et al. Effects of local chemotherapy and immunotherapy on the recurrence and progression of superficial bladder cancer: an MRC study. Eur Urol . 1988; 14:367-70. [PubMed 3139417]
108. MRC Working Party on Urological Cancer, London. The effect of intravesical thiotepa on the recurrence rate of newly diagnosed superficial bladder cancer. Br J Urol . 1985; 57:680-5. [PubMed 2867800]
109. Raghaven D, Huben R. Management of bladder cancer. Curr Prob Cancer . 1995; 19:1-64.
110. Scher HI, Shipley WU, Herr HW. Cancer of the bladder. In: DeVita VT Jr, Hellman S, Rosenberg SA eds. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1997:1300-22.
111. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther . 2000; 42:83-92. [PubMed 10994034]
112. Smith JA Jr, Labasky RF, Cockett ATK et al. Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association. J Urol . 1999; 162:1697-701. [PubMed 10524909]
113. Reviewers' comments (personal observations) on bladder cancer.
114. Kamat AM, Lamm DL. Intravesical therapy for superficial bladder cancer. Infect Urol . 1999; 12:37-45.
115. Immunex. Thioplex® (thiotepa for injection 15 mg/vial) prescribing information. Seattle, WA; 2000 Oct.