Dosing and uses of Cisplatin
Adult dosage forms and strengths
injectable solution
- 1mg/mL
Metastatic Testicular Tumors
Usual dose in combination with other approved chemotherapeutic agents is 20 mg/m²/day IV for 5 days/cycle
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Advanced Bladder Cancer
50-70 mg/m² IV cycle q3-4Weeks, depending on prior radiation therapy or chemotherapy; for heavily pretreated patients, give 50 mg/m²/cycle initially; repeat q4Weeks
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Metastatic Ovarian Carcinoma
75-100 mg/m² IV per cycle q4Weeks with cyclophosphamide (600 mg/m² IV q4Weeks); administer sequentially
Off-label: 90-270 mg/m² intraperitoneal; retain for 4 hr before draining; repeat q3Weeks (may coadminister systemic Na thiosulfate)
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Cancers (Off-label)
Cancer of cervix, endometrium, prostate, esophagus, kidney; non-small cell lung cancer; head & neck squamous cell cancer; osteogenic sarcomas; bone marrow transplants
75-100 mg/m² IV q4Weeks when used with cyclophosphamide
100 mg/m² IV q4Weeks as single agent
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Renal Impairment
CrCl 10-50 mL/min: Decrease dose 50%
CrCl <10 mL/min: Contraindicated
Metastatic Osteogenic Sarcoma (Orphan)
Liposomal cisplatin for inhalation: Treatment of osteogenic sarcoma metastatic to the lung
Orphan indication sponsor
- Transave, Inc; 11 Deer Park Drive, Suite 117; Monmouth Junction, NJ 08852-1923
Ovarian Cancer (Orphan)
Liposomal ciplatin: Treatment of ovarian cancer
Orphan indication sponsor
- Transave, Inc; 11 Deer Park Drive, Suite 117; Monmouth Junction, NJ 08852-1923
Squamous Cell Carcinoma (Orphan)
Cisplatin with epinephrine: Treatment of squamous cell carcinoma of the head and neck
Orphan indication sponsor
- Matrix Pharmaceutical, Inc; 34700 Campus Drive; Fremont, CA 94555-3612
Malignant Melanoma (Orphan)
Cisplatin with epinephrine: Treatment of metastatic malignant melanoma
Orphan indication sponsor
- Matrix Pharmaceutical, Inc; 34700 Campus Drive; Fremont, CA 94555-3612
Oral Cancers (Orphan)
ChemoThin wafer: Orphan designation for treatment of anatomically accessible oral cancers (lip, tongue, gum, floor of mouth, salivary gland, and other oral cavity)
Sponsor
- Privo Technologies; 13 Bristol Street, Unit #1; Cambridge, Massachusetts 02141
Anal Cancer (Orphan)
Orphan designation for treatment of anal cancer
Sponsor
- Privo Technologies; 13 Bristol Street Unit #1; Cambridge, Massachusetts 02141
Monitor
CBC; audiometric testing before each dose
Pediatric dosage forms and strengths
injectable solution
- 1mg/mL
Osteogenic Sarcoma/Neuroblastoma (Off-label)
90 mg/m² IV q3Weeks OR 30 mg/m² IV qWeek
Brain Tumors, Recurrent (Off-label)
60 mg/m² IV qDay for 2 consecutive days q3-4Weeks
Other Information
Verify any cisplatin dose exceeding 100 mg/m² per regimen
Geriatric dosage forms and strengths
Monitor therapy closely; elderly maybe more susceptible to nephrotoxicity and peripheral neuropathy
Metastatic Testicular Tumors
Usual dose in combination with other approved chemotherapeutic agents is 20 mg/m²/day IV for 5 days/cycle
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Advanced Bladder Cancer
50 -70 mg/m² IV cycle q3-4Weeks, depending on prior radiation therapy or chemotherapy; for heavily pretreated patients, give 50 mg/m²/cycle initially; repeat q4Weeks
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Metastatic Ovarian Carcinoma
75-100 mg/m² IV per cycle q4Weeks with cyclophosphamide (600 mg/m² IV q4Weeks); administer sequentially
Unlabeled: 90-270 mg/m² intraperitoneal; retain for 4 hr before draining; repeat q3Weeks (may coadminister systemic Na thiosulfate)
Pretreatment hydration: 1-2 L fluid infused for 8-12 hours before doseMay use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Cisplatin adverse (side) effects
>10%
Nausea (76-100%)
Vomiting (76-100%)
Nephrotoxicity (28-36%)
Ototoxicity, especially in children (31%)
Myelosuppression (25-30%)
Anaphylaxis (1-20%)
Alopecia
Frequency not defined
Cerebral herniation
Encephalopathy
Leukoencephalopathy and reversible posterior leukoencephalopathy syndrome
Seizure
Peripheral neuropathy (dose and duration dependent)
Diarrhea
Electrolyte changes
Hyperuricemia
Hepatotoxicity
Local tissue irritation
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Severe nephrotoxicity, myelosuppression, and nausea and vomiting are dose related
Significant ototoxicity, manifested by tinnitus and occasionally deafness, reported in children
Anaphylactic-like reactions have occurred. Facial edema, bronchoconstriction, tachycardia, and hypotension may occur within minutes of cisplatin administration
Failure to differentiate daily doses from total dose per treatment cycle may result in cisplatin overdose
Contraindications
Hypersensitivity to cisplatin, other platinum compounds
Severe myelosuppression, renal impairment, hearing impairment
Pregnancy, lactation
Cautions
Irritant; injection site reactions may occur during administration; use extravasation precautions
Avoid aluminum needles/equipment
Pediatric patients, hearing impairment, neuropathy, neuromuscular disease, with neurotoxic agents, with ototoxic agents, elderly
Risk of cumulative nephrotoxicity (exacerbated by aminoglycoside antibiotics); renal toxicity becomes more prolonged and severe with repeated courses; renal function must return to normal before administering another dose
Myelosuppression occurs in 25-30%; nadirs in circulating platelets and leukocytes occur between days 18-23 (range 7.5-45) with most patients recovering by day 39; elderly may be more susceptible to myelosuppression
Cardiac abnormalities, hiccups, elevated serum amylase, rash, alopecia, malaise, asthenia, and dehydration have been reported
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: excreted in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cisplatin
Mechanism of action
Platinum coordination compound that inhibits DNA synthesis; cross-links and denatures strands of DNA; disrupts DNA function by covalently binding to DNA bases; can also produce DNA intrastrand cross-linking and breakage
Not a true alkylating agent
Pharmacokinetics
Half-life elimination (terminal): 24hr to 47 days
Protein bound: >90%
Excretion: Urine (90%); feces (10%)
Clearance: 15 L/hr/m²
Vd: 11 L/m²
Administration
IV Incompatibilities
Solution: Na-bicarb 5%, D5W(?)
Additive: fluorouracil, mesna, paclitaxel(?), thiotepa
Y-site: amifostine, amphotericin B cholesteryl-SO4, cefepime, piperacillin/tazobactam, thiotepa
IV Compatibilities
Solution: dextrose-saline, NS, 1/2NS, other saline concentrations
Additive: carboplatin, cyclophosphamide w/ etoposide, etoposide, floxuridine, floxuridine w/ leucovorin, hydroxyzine, ifosfamide, leucovorin, MgSO4, mannitol, ondansetron
Syringe: bleomycin, cyclophosphamide, doxapram, doxorubicin, droperidol, fluorouracil, furosemide, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine
Y-site (partial list): allopurinol, aztreonam, bleomycin, chlorpromazine, cladribine, cyclophophamide, dexamethasone Na-succinate, diphenhydramine, doxorubicin, doxorubicin liposomal, etoposide phosphate, filgrastim, fludarabine, fluorouracil, furosemide, gemcitabine, granisetron, heparin, leucovorin, linezolid, lorazepam, melphalan, methotrexate, methylprednisolone Na-succinate, metoclopramide, mitomycin, morphine, ondansetron, paclitaxel, prochlorperazine edisylate, propofol, sargramostim, vinblastine, vincristine, vinorelbine
IV Preparation
Further dilution stability is dependent on chloride ion concentration & should be mixed in solutions of NS (at least 0.3% NaCl)
Further dilution in NS, D5/½NS or D5/NS to a concentration of 0.05-2 mg/mL are stable for 72 hr at 4-25°C in combination with mannitoL
May administer 12.5-50 g mannitol/L
Standard dilution: dose/250-1000 mL NS, D5W/NS or D5/½Ns
IV Administration
Perform pretreatment hydration
Do not use aluminum-containing needles or IV administration sets that may come in contact with carboplatin (aluminum can react causing precipitate formation & loss of potency)
Administration rate has varied from a 15-120 min infusion, 1 mg/min infusion, 6-8 hr infusion, 24 hr infusion, or per protocoL
Maximum rate of infusion: 1 mg/min in patients with CHF
When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before platinum derivatives to limit myelosuppression & to enhance efficacy
Extravasation Management
Large extravasations (>20 mL) of concentrated solutions (>0.5 mg/mL) produce tissue necrosis
Tx is not recommended unless a large amount of highly concentrated solution is extravasated
Mix 4 mL of 10% sodium thiosulfate with 6 mL SWI; inject 1-4 mL through existing IV line cannula; administer 1 mL for each mL extravasated; inject SC if needle is removed
Storage
Store intact vials at 15-25°C (59-77°F)
Protect from light
