CISPLATIN 
Pronounciation
- (sis-PLAH-tin)
Trade Name(s)
- CDDP
Verify nonpregnancy status. Baseline studies indicated; see Monitor.
Prehydration required; see Precautions and Monitor. See Dose Adjustments. May be given in combination with amifostine to reduce nephrotoxicity and neurotoxicity of cisplatin. See amifostine monograph. Administration as a 6- to 8-hour infusion with intravenous hydration and mannitol has been used to reduce nephrotoxicity. Doses greater than 100 mg/M2 once every 3 to 4 weeks are rarely used.
Used in combination with other approved chemotherapeutic agents. 20 mg/M2 daily for 5 days per cycle.
75 to 100 mg/M2 on Day 1 every 4 weeks. Used in combination with cyclophosphamide (Cytoxan) 600 mg/M2 IV on Day 1 every 4 weeks. Another regimen (unlabeled in cisplatin prescribing information) uses paclitaxel 135 mg/M2 (as a 24-hour infusion) followed by cisplatin 75 mg/M2. Both agents are given once every 3 weeks for 6 courses. See paclitaxel monograph; premedication required. Used as a single agent, the dose of cisplatin is 100 mg/M2 every 4 weeks.
First-line treatment of ovarian cancer (unlabeled in cisplatin prescribing information):
Given in combination with paclitaxel as follows: give paclitaxel 135 mg/M2 as an infusion over 24 hours. Follow with cisplatin 75 mg/M2 as an infusion over 6 to 8 hours. Repeat every 3 weeks. See paclitaxel monograph; premedication required. Other dose combinations and infusion times are being used.
50 to 70 mg/M2 once every 3 to 4 weeks. 50 mg/M2 is recommended once every 4 weeks for patients heavily pretreated with radiation or chemotherapy. Numerous other doses and combinations are used.
Non–small-cell lung cancer (unlabeled in cisplatin prescribing information):
Given in combination with gemcitabine as follows: gemcitabine 1,000 mg/M2 as an infusion on Days 1, 8, and 15 of each 28-day cycle. Follow the gemcitabine infusion on Day 1 with cisplatin 100 mg/M2. See gemcitabine monograph; other dosing schedules are in use. Another regimen uses a combination of paclitaxel and cisplatin as follows: paclitaxel 135 mg/M2 as an infusion over 24 hours followed by cisplatin 75 mg/M2 over 6 to 8 hours. Repeat every 3 weeks. See paclitaxel monograph; premedication required. Also used with docetaxel 75 mg/M2 infused over 1 hour followed immediately by an infusion of cisplatin 75 mg/M2 over 30 to 60 minutes. Repeat every 3 weeks. See docetaxel monograph; premedication required.
All doses adjusted based on prior radiation therapy or chemotherapy. ■ Repeat doses may not be given unless SCr is below 1.5 mg/100 mL and/or BUN is below 25 mg/100 mL. Renal toxicity becomes more prolonged and severe with repeated courses. Renal function must return to normal before next dose is given. ■ Platelets should be 100,000/mm3 and leukocytes 4,000/mm3; verify auditory acuity as within normal limits. ■ Dosing should be cautious in the elderly. Lower-end initial doses may be indicated. Consider decrease in cardiac, hepatic, and renal function; concomitant disease; or other drug therapy; see Elderly.
Specific techniques required; see Precautions.
Available in liquid form, 1 mg/mL. Withdraw desired dose. Immediately before use, manufacturer recommends diluting a single dose in 2 liters of D5½NS or D51/3NS containing 37.5 Gm of mannitol. Do not use D5W. Will decompose if adequate chloride ion not available. Is also diluted in smaller amounts of NS (100 to 500 mL). Do not use needles or IV tubing with aluminum parts to administer; a precipitate will form, and potency will decrease. See Monitor for additional optional additives.
Cisplatin remaining in multidose vial is stable at CRT for 28 days protected from light or 7 days under fluorescent light. Do not refrigerate. Protect from light if it will not be used within 6 hours.
Manufacturer states, “Do not use needles, IV sets, or equipment containing aluminum.” Aluminum reacts with cisplatin, causing precipitate formation and loss of potency. A precipitate will form if reconstituted solutions are refrigerated.
Other sources suggest specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Administer as a slow IV infusion; should not be given as a rapid IV injection. Rates vary based on protocol. Manufacturer suggests administering each 1 liter of infusion solution over 3 to 4 hours. Give total dose (2 liters) over 6 to 8 hours. Rate must be sufficient to maintain hydration and diuresis. Infusion times of 30 to 120 minutes are common, but infusion time has also been extended to 24 hours/dose. One source recommends a maximum rate not to exceed 1 mg/min. Too-rapid administration increases nephrotoxicity and ototoxicity.
A heavy metal complex (platinum and chloride atoms). Has properties similar to alkylating agents and is cell-cycle nonspecific. Inhibits DNA synthesis by formation of DNA cross-links. Concentration is highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen. Heavily protein bound. Only one-fourth to one-half of the drug is excreted in the urine by the end of 5 days. Platinum may be present in tissues for as long as 180 days after the last administration. Secreted in breast milk.
Treatment of metastatic testicular tumors; used in combination therapy with other approved chemotherapy agents in patients who have already received appropriate surgical and/or radiotherapeutic procedures. ■ Treatment of metastatic ovarian tumors; used in combination therapy with other approved chemotherapy agents in patients who have already received appropriate surgical and/or radiotherapeutic procedures. ■ Used as a single agent as secondary treatment in patients with metastatic ovarian tumors refractory to standard chemotherapy who have not previously received cisplatin therapy. ■ Used as a single agent for treatment of patients with transitional cell bladder cancer that is no longer amenable to local treatment such as surgery and/or radiotherapy. ■ Is used in specific combinations with other chemotherapeutic drugs.
First-line therapy for treatment of advanced cancer of the ovary in combination with paclitaxel. ■ First-line treatment of patients with inoperable, locally advanced, or metastatic non–small-cell lung cancer (NSCLC) in combination with gemcitabine, paclitaxel, or docetaxel. ■ Treatment of cancers of the brain, adrenal cortex, breast, cervix, uterus, endometrium, head and neck, esophagus, lung, and liver; osteogenic sarcomas; and numerous other malignancies.
Hypersensitivity to cisplatin or other platinum-containing compounds, myelosuppressed patients, pre-existing impaired renal function, or hearing deficit.
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Administered by or under the direction of the physician specialist.■ Adequate facilities and emergency resuscitation equipment and supplies must always be available.■ Renal toxicity can be cumulative and may be severe.■ Other major dose-related toxicities include myelosuppression, nausea, and vomiting.■ Ototoxicity (tinnitus, loss of high-frequency hearing, and/or deafness) can be significant and may be more pronounced in pediatric patients.■ Anaphylaxis has been reported and may occur within minutes of cisplatin administration.■ Labeling changed to read, “Doses greater than 100 mg/M2/cycle once every 3 to 4 weeks are rarely used.” This is an effort to eliminate serious errors resulting from confusion with carboplatin. Flip-off seal on vial now says, “Call Dr. if dose greater than 100 mg/M2/cycle.” ■ Neuropathies may occur with higher doses, greater frequency of average doses, or prolonged therapy. Usually occur after prolonged therapy but have been reported after a single dose. If symptoms of neuropathy are observed, discontinue cisplatin. ■ See Elderly.
Obtain baseline CBC, SCr, BUN, CrCl and calcium, magnesium, potassium, and sodium levels. Repeat CBC weekly and other listed labs before each subsequent cycle. ■ Hydrate patient with 1 to 2 L of infusion fluid for 8 to 12 hours before cisplatin administration. Urine output should exceed 100 to 150 mL/hr. ■ Maintain adequate hydration and urine output of at least 100 to 200 mL/hr for 24 hours after each dose. ■ Nausea and vomiting are frequently severe and prolonged (up to a week). May begin within 1 to 4 hours of administration or may be delayed. Prophylactic administration of antiemetics recommended. Fosaprepitant (Emend), ondansetron (Zofran), metoclopramide (Reglan), or dexamethasone are effective in most patients. ■ Ototoxicity is cumulative; test hearing before administration and regularly during treatment. Ototoxicity increased in pediatric patients. ■ Monitor uric acid levels before and during treatment and maintain hydration. Allopurinol and alkalinization of urine may be indicated. ■ Monitor for anaphylactic-like reactions (e.g., bronchoconstriction, facial edema, hypotension, tachycardia).■ Monitor liver function periodically. ■ Perform neurologic exams on a regular basis. Neuropathy may present as paresthesias, areflexia, and loss of proprioception and vibratory sensation. ■ Replace depleted electrolytes as necessary. ■ Observe closely for signs of infection. Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Monitor infusion site carefully during infusion; local soft tissue toxicity has been reported with extravasation. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood).
Effective birth control recommended. ■ See Appendix D.
Category D: avoid pregnancy; can cause fetal harm. Has a mutagenic potential. ■ Discontinue breast-feeding. ■ Safety and effectiveness for use in pediatric patients not established. ■ Ototoxicity increased in pediatric patients. All pediatric patients should have audiometric monitoring performed before initiation of therapy, before each dose, and for several years after therapy.
Dose selection should be cautious; see Dose Adjustments. ■ Response (e.g., effectiveness) is similar to younger adults, but length of survival may be shorter. ■ Incidence of myelosuppression (e.g., severe leukopenia, neutropenia, thrombocytopenia), infectious complications, nephrotoxicity, and peripheral neuropathy may be increased.
Ototoxicity and nephrotoxicity are potentiated with other ototoxic or nephrotoxic agents (e.g., aminoglycosides and loop diuretics). Concurrent use not recommended. ■ Serum levels of anticonvulsant agents (e.g., phenytoin) may become subtherapeutic when used concurrently with cisplatin. Monitor anticonvulsant levels; increased doses may be indicated. ■ Bone marrow toxicity increased with other antineoplastic agents and/or radiation therapy.■ Synergistic with etoposide; may be beneficial. ■ May affect renal excretion and increase toxicity of many drugs (e.g., bleomycin, methotrexate).■ Response duration may be shortened with concurrent use of pyridoxine (vitamin B6) and altretamine.■ Do not administer live virus vaccines to patients receiving antineoplastic agents.
Are frequent; can occur with the initial dose and will become more severe with succeeding doses. Dose-related and cumulative renal insufficiency, including renal failure, is the major dose-limiting toxicity (often noted during the second week following a dose). Acute leukemia, alopecia, anaphylaxis (facial edema, hypotension, tachycardia, and wheezing within minutes of administration), asthenia, cardiac abnormalities, dehydration, diarrhea, electrolyte disturbances (hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia), elevated serum amylase, hemolytic anemia, hepatotoxicity, hyperuricemia, malaise, myelosuppression, nausea and vomiting (acute or delayed), syndrome of inappropriate antidiuretic hormone secretion (SIADH), neurotoxicity (including peripheral neuropathy that may be reversible, leukoencephalopathy, and reversible posterior leukoencephalopathy syndrome [RPLS]), ocular toxicity (e.g., blurred vision, cerebral blindness, optic neuritis, papilledema), ototoxicity including tinnitus and hearing loss in the high-frequency range, peripheral neuropathy (may be irreversible), vascular toxicities (e.g., cerebral arteritis, CVA, MI, or thrombotic microangiopathy [hemolytic-uremic syndrome (HUS)]), and vestibular toxicity.
Deafness, intractable nausea and vomiting, kidney failure, liver failure, neuritis, ocular toxicity, significant myelosuppression, and death.
Notify physician of all side effects. Cisplatin may have to be discontinued permanently or until recovery. Symptomatic and supportive treatment is indicated. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes) and/or blood modifiers (e.g., darbepoetin alfa [Aranesp], epoetin alfa [Epogen], filgrastim [Neupogen, Zarxio], pegfilgrastim [Neulasta], sargramostim [Leukine]) may be indicated to treat bone marrow toxicity. Pretreatment with amifostine may reduce nephrotoxic, neurotoxic, and hematologic effects. Treat anaphylaxis with epinephrine, corticosteroids, oxygen, and antihistamines. There is no specific antidote. Hemodialysis appears to have little effect on removing platinum from the body because of the rapid and high degree of protein binding.