carboplatin injection CLINICAL STUDIES

Prescribing Information

CLINICAL STUDIES

Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer

In two prospectively randomized, controlled studies conducted by the National Cancer Institute of Canada, Clinical Trials Group (NCIC), and the Southwest Oncology Group (SWOG), 789 chemotherapy naive patients with advanced ovarian cancer were treated with carboplatin or cisplatin, both in combination with cyclophosphamide every 28 days for six courses before surgical reevaluation. The following results were obtained from both studies:

Comparative Efficacy:

Overview of Pivotal Trials
	NCIC	SWOG
Number of patients randomized	447	342
Median age (years)	60	62
Dose of cisplatin	75 mg/m2	100 mg/m2
Dose of carboplatin	300 mg/m2	300 mg/m2
Dose of cyclophosphamide	600 mg/m2	600 mg/m2
Residual tumor <2 cm (number of patients)	39% (174/447)	14% (49/342)

Clinical Response in Measurable Disease Patients
	NCIC	SWOG
Carboplatin (number of patients)	60% (48/80)	58% (48/83)
Cisplatin (number of patients)	58% (49/85)	43% (33/76)
95% C.I. of difference (Carboplatin - Cisplatin)	(-13.9%, 18.6%)	(-2.3%, 31.1%)

Pathologic Complete Response*
	NCIC	SWOG
* 114 Carboplatin and 109 Cisplatin patients did not undergo second look surgery in NCIC study. 90 Carboplatin and 106 Cisplatin patients did not undergo second look surgery in SWOG study.
Carboplatin (number of patients)	11% (24/224)	10% (17/171)
Cisplatin (number of patients)	15% (33/223)	10% (17/171)
95% C.I. of difference (Carboplatin - Cisplatin)	(-10.7%, 2.5%)	(-6.9%, 6.9%)

Progression-Free Survival (PFS)
	NCIC	SWOG
* Kaplan-Meier Estimates Unrelated deaths occurring in the absence of progression were counted as events (progression) in this analysis. † Analysis adjusted for factors found to be of prognostic significance were consistent with unadjusted analysis.
Median
Carboplatin	59 weeks	49 weeks
Cisplatin	61 weeks	47 weeks
2-year PFS*
Carboplatin	31%	21%
Cisplatin	31%	21%
95% C.I. of difference (Carboplatin - Cisplatin)	(-9.3, 8.7)	(-9.0, 9.4)
3-year PFS*
Carboplatin	19%	8%
Cisplatin	23%	14%
95% C.I. of difference (Carboplatin - Cisplatin)	(-11.5, 4.5)	(-14.1, 0.3)
Hazard Ratio†	1.10	1.02
95% C.I. (Carboplatin - Cisplatin)	(0.89, 1.35)	(0.81, 1.29)

Survival
	NCIC	SWOG
* Kaplan-Meier Estimates † Analysis adjusted for factors found to be of prognostic significance were consistent with unadjusted analysis.
Median
Carboplatin	110 weeks	86 weeks
Cisplatin	99 weeks	79 weeks
2-year Survival*
Carboplatin	51.9%	40.2%
Cisplatin	48.4%	39.0%
95% C.I. of difference (Carboplatin - Cisplatin)	(-6.2, 13.2)	(-9.8, 12.2)
3-year Survival*
Carboplatin	34.6%	18.3%
Cisplatin	33.1%	24.9%
95% C.I. of difference (Carboplatin - Cisplatin)	(-7.7, 10.7)	(-15.9, 2.7)
Hazard Ratio†	0.98	1.01
95% C.I. (Carboplatin - Cisplatin)	(0.78, 1.23)	(0.78, 1.30)

Comparative Toxicity

The pattern of toxicity exerted by the carboplatin containing regimen was significantly different from that of the cisplatin-containing combinations. Differences between the two studies may be explained by different cisplatin dosages and by different supportive care.

The carboplatin-containing regimen induced significantly more thrombocytopenia and, in one study, significantly more leukopenia and more need for transfusional support. The cisplatin-containing regimen produced significantly more anemia in one study. However, no significant differences occurred in incidences of infections and hemorrhagic episodes.

Non-hematologic toxicities (emesis, neurotoxicity, ototoxicity, renal toxicity, hypomagnesemia, and alopecia) were significantly more frequent in the cisplatin-containing arms.

ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER NCIC STUDY
		Carboplatin Arm Percent*	Cisplatin Arm Percent*	P-Values†
* Values are in percent of evaluable patients † ns = not significant, p>0.05 ‡ May have been affected by cyclophosphamide dosage delivered
Bone Marrow
Thrombocytopenia	<100,000/mm3	70	29	<0.001
	<50,000/mm3	41	6	<0.001
Neutropenia	<2,000 cells/mm3	97	96	ns
	<1,000 cells/mm3	81	79	ns
Leukopenia	<4,000 cells/mm3	98	97	ns
	<2,000 cells/mm3	68	52	0.001
Anemia	<11 g/dL	91	91	ns
	<8 g/dL	18	12	ns
Infections		14	12	ns
Bleeding		10	4	ns
Transfusions		42	31	0.018
Gastrointestinal
Nausea and vomiting		93	98	0.010
Vomiting		84	97	<0.001
Other GI side effects		50	62	0.013
Neurologic
Peripheral neuropathies		16	42	<0.001
Ototoxicity		13	33	<0.001
Other sensory side effects		6	10	ns
Central neurotoxicity		28	40	0.009
Renal
Serum creatinine elevations		5	13	0.006
Blood urea elevations		17	31	<0.001
Hepatic
Bilirubin elevations		5	3	ns
SGOT elevations		17	13	ns
Alkaline phosphatase elevations		-	-	-
Electrolytes loss
Sodium		10	20	0.005
Potassium		16	22	ns
Calcium		16	19	ns
Magnesium		63	88	<0.001
Other side effects
Pain		36	37	ns
Asthenia		40	33	ns
Cardiovascular		15	19	ns
Respiratory		8	9	ns
Allergic		12	9	ns
Genitourinary		10	10	ns
Alopecia ‡		50	62	0.017
Mucositis		10	9	ns

ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER SWOG STUDY
		Carboplatin Arm Percent*	Cisplatin Arm Percent*	P-Values†
* Values are in percent of evaluable patients † ns = not significant, p>0.05 ‡ May have been affected by cyclophosphamide dosage delivered
Bone Marrow
Thrombocytopenia	<100,000/mm3	59	35	<0.001
	<50,000/mm3	22	11	0.006
Neutropenia	<2,000 cells/mm3	95	97	ns
	<1,000 cells/mm3	84	78	ns
Leukopenia	<4,000 cells/mm3	97	97	ns
	<2,000 cells/mm3	76	67	ns
Anemia	<11 g/dL	88	87	ns
	<8 g/dL	8	24	<0.001
Infections		18	21	ns
Bleeding		6	4	ns
Transfusions		25	33	ns
Gastrointestinal
Nausea and vomiting		94	96	ns
Vomiting		82	91	0.007
Other GI side effects		40	48	ns
Neurologic
Peripheral neuropathies		13	28	0.001
Ototoxicity		12	30	<0.001
Other sensory side effects		4	6	ns
Central neurotoxicity		23	29	ns
Renal
Serum creatinine elevations		7	38	<0.001
Blood urea elevations		-	-	-
Hepatic
Bilirubin elevations		5	3	ns
SGOT elevations		23	16	ns
Alkaline phosphatase elevations		29	20	ns
Electrolytes loss
Sodium		-	-	-
Potassium		-	-	-
Calcium		-	-	-
Magnesium		58	77	<0.001
Other side effects
Pain		54	52	ns
Asthenia		43	46	ns
Cardiovascular		23	30	ns
Respiratory		12	11	ns
Allergic		10	11	ns
Genitourinary		11	13	ns
Alopecia ‡		43	57	0.009
Mucositis		6	11	ns

Use as a Single Agent for Secondary Treatment of Advanced Ovarian Cancer

In two prospective, randomized controlled studies in patients with advanced ovarian cancer previously treated with chemotherapy, carboplatin achieved six clinical complete responses in 47 patients. The duration of these responses ranged from 45 to 71 + weeks.

Medication Guide

PATIENT INFORMATION

Rx only

Read this entire leaflet carefully. Keep it for future reference.

Carboplatin Injection

This information will help you learn more about Carboplatin Injection. It cannot, however, cover all the possible warnings or side effects relating to Carboplatin Injection, and it does not list all of the benefits and risks of Carboplatin Injection. Your doctor should always be your first choice for detailed information about your medical condition and your treatment. Be sure to ask your doctor about any questions you may have.

What is cancer?

Under normal conditions, the cells in your body divide and grow in an orderly, controlled fashion. Cell division and growth are necessary for the human body to perform its functions and to repair itself. Cancer cells are different from normal cells because they are not able to control their own growth. The reasons for this abnormal growth are not yet fully understood.

A tumor is a mass of unhealthy cells that are dividing and growing fast and in an uncontrolled way. When a tumor invades surrounding healthy body tissue it is known as a malignant tumor. A malignant tumor can spread (metastasize) from its original location to other parts of the body.

What is Carboplatin Injection?

Carboplatin Injection is a medicine that is used to treat cancer of the ovaries. It acts by interfering with the division of rapidly multiplying cells, particularly cancer cells.

Who should not take Carboplatin Injection?

Treatment with Carboplatin Injection is not recommended if you:

•: are allergic to Carboplatin Injection or other platinum-containing products;
•: have a weakened blood-forming system (bone marrow depression) or significant bleeding;
•: are pregnant, intend to become pregnant, or are breast-feeding a baby.

How is Carboplatin Injection used?

Only a professional experienced in the use of cancer drugs should give you this medication. Carboplatin Injection is given by dripping the medicine slowly and directly into a vein (intravenous infusion) for 15 minutes or longer. Your doctor will determine the dose of Carboplatin Injection for you based on your weight, height, and kidney function. Carboplatin Injection may be given alone or with other drugs. Treatment is usually repeated every four weeks for a number of cycles.

Before and after Carboplatin Injection treatment, your doctor may give you medication to lessen the nausea and vomiting associated with this cancer treatment.

What should you tell your doctor before starting treatment with Carboplatin Injection?

Discuss the benefits and risks of Carboplatin Injection with your doctor before beginning treatment.

Be sure to inform your doctor:

•: If you are allergic to Carboplatin Injection or other platinum containing products;
•: If you are or intend to become pregnant, since Carboplatin Injection may harm the developing fetus. It is important to use effective birth control while you are being treated with Carboplatin Injection;
•: If you are breast-feeding, since nursing infants may be exposed to Carboplatin Injection in this way;
•: If you are taking other medicines, including all prescription and non prescription (over-the-counter) drugs, since Carboplatin Injection may affect the action of other medicines;
•: If you have any other medical problems, especially chicken pox (including recent exposure to adults or children with chicken pox), shingles, hearing problems, infection, or kidney disease, since treatment with Carboplatin Injection increases the risk and severity of these conditions.

What should I avoid while taking Carboplatin Injection?

If you are pregnant or think you might be pregnant, or if you are breast feeding, let your doctor know right away. Carboplatin Injection may harm your developing fetus or breast-feeding baby. If you are a woman of childbearing age, you should use birth control to avoid getting pregnant while you are taking Carboplatin Injection.

You should avoid contact with adults and children who have infections, and tell your doctor right away if you show signs of infection such as cough, fever, and/or chills.

Also, while you are being treated with Carboplatin Injection or after you stop treatment, first check with your doctor before getting any immunizations (vaccinations). Avoid contact with adults or children who have received oral polio vaccine since they can pass the polio virus to you.

What are the possible side effects of Carboplatin Injection?

Carboplatin Injection may cause unwanted effects, particularly because Carboplatin Injection interferes with the growth of normal cells as well as cancer cells. For example, the occurrence of another cancer (secondary malignancy) has been reported in patients receiving cancer chemotherapy with multiple drugs. It is not always possible to tell whether such effects are caused by Carboplatin Injection, another drug you may be taking, or your illness. Because some of these effects may be serious, you will need close medical supervision during treatment with Carboplatin Injection.

The most serious side effects of Carboplatin Injection are:

•: bleeding and reduced blood cells, including reduced red blood cells (anemia) and platelets (needed for proper blood clotting), which may be severe enough to require blood transfusion. You should tell your doctor right away if you notice any unusual bruising or bleeding, including black tarry stools or blood in the urine.
•: infection – Carboplatin Injection can temporarily lower the number of white blood cells in your blood, increasing the risk of infection;
•: life-threatening allergic reaction – during and after treatment the doctor or nurse will observe you carefully for signs of allergic reaction;
•: kidney and liver problems;
•: loss of hearing or ringing in the ears;

Contact your doctor right away if you experience any of these effects, or notice effects that worry you or are troublesome.

Of the less serious side effects associated with Carboplatin Injection treatment, the most common are nausea, vomiting, diarrhea, loss of appetite, hair loss and numbness, tingling, burning, or pain in the hands or feet.

This medicine was prescribed for your particular condition. It must be given under close medical supervision by a doctor trained in the use of drugs for the treatment of cancer. This summary does not include everything there is to know about Carboplatin Injection. Medicines are sometimes prescribed for purposes other than those listed in patient leaflets. If you have questions or concerns, or want more information about Carboplatin Injection, your physician and pharmacist have the complete prescribing information upon which this information is based. You may want to read it and discuss it with your doctor. Remember, no written summary can replace careful discussion with your doctor.

Distributed by Hospira, Inc. Lake Forest, IL 60045

LAB-1016-2.0

Revised: 4/2018

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