(KAR boe pla tin)
Ovarian cancer: Initial treatment of advanced ovarian cancer in combination with other established chemotherapy agents; palliative treatment of recurrent ovarian cancer after prior chemotherapy, including cisplatin-based treatment
History of severe allergic reaction to carboplatin, cisplatin, other platinum-containing formulations, mannitol, or any component of the formulation; should not be used in patients with severe bone marrow depression or significant bleeding
Carboplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.
Bone marrow suppression:Bone marrow suppression is dose related and may be severe, resulting in infection or bleeding. Anemia may be cumulative and may require transfusion support.
Vomiting:Vomiting is a frequent drug-related side effect.
Hypersensitivity reactions:Anaphylactic-like reactions to carboplatin have been reported and may occur within minutes of carboplatin administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms.
Note: Doses for adults are commonly calculated by the target AUC using the Calvert formula, where Total dose (mg) = Target AUC x (GFR + 25). If estimating glomerular filtration rate (GFR) instead of a measured GFR, the Food and Drug Administration (FDA) recommends that clinicians consider capping estimated GFR at a maximum of 125 mL/minute to avoid potential toxicity. Carboplatin is associated with a moderate emetic potential in adult patients; antiemetics are recommended to prevent nausea and vomiting (Basch, 2011; Roila, 2010).
Ovarian cancer, advanced:Manufacturer 's labeling: IV: 360 mg/m2 every 4 weeks (as a single agent) or 300 mg/m2 every 4 weeks (in combination with cyclophosphamide) or Target AUC 4 to 6 (single agent; in previously-treated patients)
Off-label dosing for advanced ovarian cancer: IV: Target AUC 5 to 7.5 every 3 weeks (in combination with paclitaxel) (Ozols, 2003; Parmar, 2003) or Target AUC 5 every 3 weeks (in combination with docetaxel) (Vasey, 2004)
Bladder cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with gemcitabine) (Bamias, 2006) or Target AUC 6 every 3 weeks (in combination with paclitaxel) (Vaughn, 2002)
Breast cancer, metastatic (off-label use): IV: Target AUC 6 every 3 weeks (in combination with trastuzumab and paclitaxel) (Robert, 2006) or Target AUC 6 every 3 weeks (in combination with trastuzumab and docetaxel) (Pegram, 2004; Valero, 2011)
Cervical cancer, recurrent or metastatic (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Pectasides, 2009) or Target AUC 5 to 6 every 4 weeks (in combination with paclitaxel) (Tinker, 2005) or 400 mg/m2 every 28 days (as a single agent) (Weiss, 1990)
Endometrial cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Pectasides, 2008) or Target AUC 2 on days 1, 8, and 15 every 28 days (in combination with paclitaxel) (Secord, 2007)
Esophageal cancer (off-label use): IV: Target AUC 2 on days 1, 8, 15, 22, and 29 for 1 cycle (in combination with paclitaxel) (van Meerten, 2006) or Target AUC 5 every 3 weeks (in combination with paclitaxel) (El-Rayes, 2004)
Head and neck cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with cetuximab) (Chan, 2005) or Target AUC 5 every 3 weeks (in combination with cetuximab and fluorouracil) (Vermorken, 2008) or 300 mg/m2 every 4 weeks (in combination with fluorouracil) (Forastiere, 1992) or Target AUC 6 every 3 weeks (in combination with paclitaxel) (Clark, 2001)
Hodgkin lymphoma, relapsed or refractory (off-label use): IV: Target AUC 5 (maximum dose: 800 mg) for 2 cycles (in combination with ifosfamide and etoposide) (Moskowitz, 2001)
Malignant pleural mesothelioma (off-label use): IV: Target AUC 5 every 3 weeks (in combination with pemetrexed) (Castagneto, 2008; Ceresoli, 2006)
Melanoma, advanced or metastatic (off-label use): IV: Target AUC 2 days on 1, 8, and 15 every 4 weeks (in combination with paclitaxel) (Rao, 2006)
Non-Hodgkin lymphomas, relapsed or refractory (off-label use): IV: Target AUC 5 (maximum dose: 800 mg) per cycle for 3 cycles (in combination with rituximab, ifosfamide and etoposide) (Kewalramani, 2004)
Non-small cell lung cancer (off-label use): IV: Target AUC 6 every 3 to 4 weeks (in combination with paclitaxel) (Ramalingam, 2008; Schiller, 2002; Strauss, 2008) or Target AUC 6 every 3 weeks (in combination with bevacizumab and paclitaxel) (Sandler, 2006) or Target AUC 5 every 3 weeks (in combination with pemetrexed) (Gronberg, 2009) or in combination with radiation therapy and paclitaxel (Belani, 2005):
Target AUC 6 every 3 weeks for 2 cycles or
Target AUC 6 every 3 weeks for 2 cycles; then target AUC 2 weekly for 7 weeks or
Target AUC 2 every week for 7 weeks; then target AUC 6 every 3 weeks for 2 cycles
Sarcomas: Ewing sarcoma, osteosarcoma (off-label uses): IV: 400 mg/m2/day for 2 days every 21 days (in combination with ifosfamide and etoposide) (van Winkle, 2005)
Small cell lung cancer (off-label use): IV: Target AUC 6 every 3 weeks (in combination with etoposide) (Skarlos, 2001) or Target AUC 5 every 3 weeks (in combination with irinotecan) (Hermes, 2008) or Target AUC 5 every 28 days (in combination with irinotecan) (Schmittel, 2006)
Testicular cancer (off-label use): IV: Target AUC 7 as a one-time dose (Oliver, 2011) or 700 mg/m2/day for 3 days beginning 5 days prior to peripheral stem cell infusion (in combination with etoposide) for 2 cycles (Einhorn, 2007)
Thymic malignancies (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Lemma, 2008)
Unknown primary adenocarcinoma (off-label use): IV: Target AUC 6 every 3 weeks (in combination with paclitaxel) (Briasoulis, 2000) or Target AUC 6 every 3 weeks (in combination with docetaxel) (Greco, 2000) or Target AUC 6 every 3 weeks (in combination with paclitaxel and etoposide) (Hainsworth, 2006) or Target AUC 5 every 3 weeks (in combination with paclitaxel and gemcitabine) (Greco, 2002)
The Calvert formula should be used to calculate dosing for elderly patients. Refer to adult dosing.
Carboplatin is associated with a high emetic potential in pediatric patients; antiemetics are recommended to prevent nausea and vomiting (Dupuis, 2011).
Central nervous system tumors (off-label use):
Glioma: IV: 175 mg/m2 weekly for 4 weeks every 6 weeks, with a 2-week recovery period between courses (in combination with vincristine) (Packer, 1997)
Neuroblastoma, localized and unresectable: IV: Children ≥10 kg: 200 mg/m2/day days 1, 2, and 3 every 21 days for 2 cycles (in combination with etoposide for 2 cycles then followed by cyclophosphamide, doxorubicin and vincristine) (Rubie, 1998) or Children <1 year: 6.6 mg/kg/day days 1, 2, and 3 (in combination with etoposide for 2 cycles, then followed by cyclophosphamide, doxorubicin, and vincristine) (Rubie, 2001)
Sarcomas: Ewing sarcoma, osteosarcoma (off-label uses): IV: 400 mg/m2/day for 2 days every 21 days (in combination with ifosfamide and etoposide) (van Winkle, 2005)
Note: Dose determination with Calvert formula uses GFR and, therefore, inherently adjusts for renal dysfunction.
The manufacturer 's labeling recommends the following dosage adjustments for single-agent therapy: Adults:
Baseline CrCl 41 to 59 mL/minute: Initiate at 250 mg/m2 and adjust subsequent doses based on bone marrow toxicity
Baseline CrCl 16 to 40 mL/minute: Initiate at 200 mg/m2 and adjust subsequent doses based on bone marrow toxicity
Baseline CrCl ≤15 mL/minute: There are no dosage adjustments provided in the manufacturer 's labeling.
The following dosage adjustments have also been recommended:
Aronoff, 2007:
Adults (Note: For dosing based on mg/m2):
GFR >50 mL/minute: No dosage adjustment is necessary
GFR 10 to 50 mL/minute: Administer 50% of the dose
GFR <10 mL/minute: Administer 25% of the dose
Hemodialysis: Administer 50% of dose
Continuous ambulatory peritoneal dialysis (CAPD): Administer 25% of dose
Continuous renal replacement therapy (CRRT): 200 mg/m2
Children:
GFR <50 mL/minute: Use Calvert formula incorporating patient 's GFR
Hemodialysis, peritoneal dialysis, continuous renal replacement therapy (CRRT): Use Calvert formula incorporating patient 's GFR
Janus, 2010: Hemodialysis: Carboplatin dose (mg) = Target AUC x 25; administer on a nondialysis day, hemodialysis should occur between 12-24 hours after carboplatin dose
There are no dosage adjustments provided in the manufacturer 's labeling; however, carboplatin undergoes minimal hepatic metabolism therefore dosage adjustment may not be needed.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Solution for injection: Manufacturer 's labeling states solution can be further diluted to concentrations as low as 0.5 mg/mL in NS or D5W; however, most clinicians generally dilute dose in either 100 mL or 250 mL of NS or D5W.
Concentrations used for desensitization vary based on protocol.
Needles or IV administration sets that contain aluminum should not be used in the preparation or administration of carboplatin; aluminum can react with carboplatin resulting in precipitate formation and loss of potency.
Carboplatin is associated with a moderate emetic potential in adult patients and a high emetic potential in pediatric patients; antiemetics are recommended to prevent nausea and vomiting (Basch, 2011; Dupuis, 2011; Roila, 2010).
Infuse over at least 15 minutes; usually infused over 15 to 60 minutes, although some protocols may require infusions up to 24 hours. When administered as a part of a combination chemotherapy regimen, sequence of administration may vary by regimen; refer to specific protocol for sequence recommendation.
Needles or IV administration sets that contain aluminum should not be used in the preparation or administration of carboplatin; aluminum can react with carboplatin resulting in precipitate formation and loss of potency.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Store intact vials at room temperature at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light. Further dilution to a concentration as low as 0.5 mg/mL is stable at room temperature (25 ‚ °C) for 8 hours in NS or D5W. Stability has also been demonstrated for dilutions in D5W in PVC bags at room temperature for 9 days (Benaji, 1994); however, the manufacturer recommends use within 8 hours due to lack of preservative. Multidose vials are stable for up to 14 days after opening when stored at 25 ‚ °C (77 ‚ °F) following multiple needle entries.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 50 mg/5 mL (5 mL); 150 mg/15 mL (15 mL); 450 mg/45 mL (45 mL); 600 mg/60 mL (60 mL)
Solution, Intravenous [preservative free]:
Generic: 50 mg/5 mL (5 mL); 150 mg/15 mL (15 mL); 450 mg/45 mL (45 mL); 600 mg/60 mL (60 mL)
Solution Reconstituted, Intravenous:
Generic: 150 mg (1 ea)
Stable in D51/4NS, D51/2NS, D5NS, D5W, NS.
Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex.
Aminoglycosides: May enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Bexarotene (Systemic): CARBOplatin may increase the serum concentration of Bexarotene (Systemic). Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Fosphenytoin-Phenytoin: Platinum Derivatives may decrease the serum concentration of Fosphenytoin-Phenytoin. Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
SORAfenib: May enhance the adverse/toxic effect of CARBOplatin. Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution. Avoid combination
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Taxane Derivatives: Platinum Derivatives may enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Consider therapy modification
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Topotecan: Platinum Derivatives may enhance the adverse/toxic effect of Topotecan. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
CBC (with differential and platelet count), serum electrolytes, serum creatinine and BUN, creatinine clearance, liver function tests; audiology evaluations (children <6 months of age)
Percentages reported with single-agent therapy.
>10%:
Central nervous system: Pain (23%)
Endocrine & metabolic: Hyponatremia (29% to 47%), hypomagnesemia (29% to 43%), hypocalcemia (22% to 31%), hypokalemia (20% to 28%)
Gastrointestinal: Vomiting (65% to 81%), abdominal pain (17%), nausea (without vomiting: 10% to 15%)
Hematologic & oncologic: Bone marrow depression (dose related and dose limiting; nadir at ~21 days with single-agent therapy), anemia (71% to 90%; grades 3/4: 21%), leukopenia (85%; grades 3/4: 15% to 26%), neutropenia (67%; grades 3/4: 16% to 21%), thrombocytopenia (62%; grades 3/4: 25% to 35%)
Hepatic: Increased serum alkaline phosphatase (24% to 37%), increased serum AST (15% to 19%)
Hypersensitivity: Hypersensitivity (2% to 16%)
Neuromuscular & skeletal: Weakness (11%)
Renal: Decreased creatinine clearance (27%), increased blood urea nitrogen (14% to 22%)
1% to 10%:
Central nervous system: Peripheral neuropathy (4% to 6%), neurotoxicity (5%)
Dermatologic: Alopecia (2% to 3%)
Gastrointestinal: Constipation (6%), diarrhea (6%), dysgeusia (1%), mucositis ( ≤1%), stomatitis ( ≤1%)
Hematologic & oncologic: Bleeding complications (5%), hemorrhage (5%)
Hepatic: Increased serum bilirubin (5%)
Infection: Infection (5%)
Ophthalmic: Visual disturbance (1%)
Otic: Ototoxicity (1%)
Renal: Increased serum creatinine (6% to 10%)
<1% (Limited to important or life-threatening): Anaphylaxis, anorexia, bronchospasm, cardiac failure, cerebrovascular accident, dehydration, embolism, erythema, febrile neutropenia, hemolytic anemia (acute), hemolytic-uremic syndrome, hypertension, hypotension, injection site reaction (pain, redness, swelling), limb ischemia (acute), malaise, metastases, pruritus, skin rash, tissue necrosis (associated with extravasation), urticaria, vision loss
In those with CrCl less than 60 mL/minute, the total body and renal clearance decreases as the CrCl decreases.
Concerns related to adverse effects:
- Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression, which may be severe, is dose related; may result in infection (due to neutropenia) or bleeding (due to thrombocytopenia); anemia may require blood transfusion. Reduce dosage in patients with bone marrow suppression; cycles should be delayed until WBC and platelet counts have recovered. Patients who have received prior myelosuppressive therapy and patients with renal dysfunction are at increased risk for bone marrow suppression. Anemia is cumulative.
- Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Anaphylactic-like reactions have been reported with carboplatin; may occur within minutes of administration. Epinephrine, corticosteroids and antihistamines have been used to treat symptoms. The risk of allergic reactions (including anaphylaxis) is increased in patients previously exposed to platinum therapy. Skin testing and desensitization protocols have been reported (Confina-Cohen, 2005; Lee, 2004; Markman, 2003).
- Liver function abnormalities: High doses (>4 times the recommended dose) have resulted in severe abnormalities of liver function tests.
- Neurotoxicity: Although peripheral neuropathy occurs infrequently, the incidence of peripheral neuropathy is increased in patients >65 years of age and those who have previously received cisplatin treatment.
- Ototoxicity: Ototoxicity may occur when administered concomitantly with aminoglycosides. Clinically significant hearing loss has been reported to occur in pediatric patients when therapy was administered at higher than recommended doses in combination with other ototoxic agents (eg, aminoglycosides). In a study of children receiving carboplatin for the treatment of retinoblastoma, those <6 months of age at treatment initiation were more likely to experience ototoxicity; long-term audiology monitoring is recommended (Qaddoumi, 2012).
- Renal toxicity: Limited potential for nephrotoxicity unless administered concomitantly with aminoglycosides.
- Vision loss: Loss of vision (usually reversible within weeks of discontinuing) has been reported with higher than recommended doses.
- Vomiting: [US Boxed Warning]: Vomiting may occur. Carboplatin is associated with a moderate emetic potential in adult patients and a high emetic potential in pediatric patients; antiemetics are recommended to prevent nausea and vomiting (Basch, 2011; Dupuis, 2011; Roila, 2010). May be severe in patients who have received prior emetogenic therapy.
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal impairment; patients with renal dysfunction are at increased risk for bone marrow suppression.
Concurrent drug therapy issues:
- Taxane derivatives: When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before the platinum derivatives (carboplatin, cisplatin) to limit myelosuppression and to enhance efficacy.
Special populations:
- Elderly: Patients >65 years of age are more likely to develop thrombocytopenia (severe) and peripheral neuropathy.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Other warnings/precautions:
- Dosing with Calvert formula: When calculating the carboplatin dose using the Calvert formula and an estimated glomerular filtration rate (GFR), the laboratory method used to measure serum creatinine may impact dosing. Compared to other methods, standardized isotope dilution mass spectrometry (IDMS) may underestimate serum creatinine values in patients with low creatinine values (eg, ≤0.7 mg/dL) and may overestimate GFR in patients with normal renal function. This may result in higher calculated carboplatin doses and increased toxicities. If using IDMS, the Food and Drug Administration (FDA) recommends that clinicians consider capping estimated GFR at a maximum of 125 mL/minute to avoid potential toxicity.
- Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
D
Embryotoxicity and teratogenicity have been observed in animal reproduction studies. May cause fetal harm if administered during pregnancy. Women of childbearing potential should avoid becoming pregnant during treatment.
Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links
Vd: 16 L (based on a dose of 300 to 500 mg/m2); into liver, kidney, skin, and tumor tissue
Minimally hepatic to aquated and hydroxylated compounds
Urine (~70% as carboplatin within 24 hours; 3% to 5% as platinum within 1 to 4 days)
CrCl >60 mL/minute: Carboplatin: 2.6 to 5.9 hours (based on a dose of 300-500 mg/m2); Platinum (from carboplatin): ≥5 days
Carboplatin: 0%; Platinum (from carboplatin): Irreversibly binds to plasma proteins
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea or mouth sores. Have patient report immediately to prescriber signs of infection, signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting), vomiting, bruising, bleeding, loss of strength and energy, hearing impairment, burning or numbness feeling, blindness, or injection site pain or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.