Efficacy

The efficacy of GEMZAR therapy* in 1st-line NSCLC has been consistently proven across a large body of phase III studies.

Data from 2 randomized clinical studies (657 patients) support the use of GEMZAR in combination with cisplatin for the first-line treatment of patients with locally advanced or metastatic NSCLC, and have generated:

• Consistent results
  GEMZAR has demonstrated proven survival, time to disease progression, and response rate benefits across comparative trials
  
  
• Comprehensive data
  GEMZAR is the most studied agent among the leading nonplatinum agents¹

Phase III studies of GEMZAR therapy* in the first-line treatment of advanced NSCLC:

* GEMZAR in combination with cisplatin
† In combination with cisplatin, is indicated for the first-line treatment of advanced or metastatic NSCLC.
‡ Is indicated as a single agent or in combination with cisplatin for the first-line treatment of advanced NSCLC.
§ Is indicated as a single agent for the treatment of locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy. The clinical trials reviewed to support the information presented in this table were found by searching the Medline, Embase, and Cancerlit databases as of September 2006. The following search items were used: NSCLC, non small or non-small, and phase 3 or phase III. Abstracts from ASCO 2001-2006, along with abstracts from ESMO 2002, 2004, and ECCO 2005, were searched individually using the same search criteria. Studies involving radiation, surgery, or second-line usage were not included.

GEMZAR demonstrated proven efficacy based on three endpoints studied in the following phase III^‡ randomized trials:

• Median survival
• Median time to disease progression
• Response rate

The data review was last conducted in September 2006. The results from these studies may not prove clinical equivalence or noninferiority.

NR = Not reported.
*GEMZAR in combination with cisplatin.

References:

1. Data on file, Eli Lilly and Company; ONC20061106B.
2. N Engl J Med. 2002;346(2):92-98.
3. GEMZAR (gemcitabine HCl for injection) [package insert]. Indianapolis, Ind: Eli Lilly and Company; 2007.
4. J Clin Oncol. 1999;17(1):12-18.

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GEMZAR^® is a registered trademark of Eli Lilly and Company. GC 50579

About GEMZAR

GEMZAR is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (stage IIIA or IIIB), or metastatic (stage IV) non-small cell lung cancer.

GEMZAR in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.

GEMZAR in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

GEMZAR is indicated as first-line treatment for patients with locally advanced (nonresectable stage II or stage III) or metastatic (stage IV) adenocarcinoma of the pancreas. GEMZAR is indicated for patients previously treated with 5-FU.

Important Safety Information

Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.

Contraindication
Known hypersensitivity to GEMZAR.

Warnings
Infusion times of GEMZAR longer than 60 minutes and more frequent than weekly dosing have been shown to increase toxicity.

Pulmonary toxicity has been reported. In cases of severe lung toxicity, GEMZAR therapy should be discontinued immediately and appropriate supportive care measures instituted.

Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of GEMZAR. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS.

Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving GEMZAR alone or in combination with other potentially hepatotoxic drugs.

GEMZAR is Pregnancy Category D. GEMZAR can cause fetal harm when administered to a pregnant woman.

Precautions
Use caution in patients with pre-existing renal impairment or hepatic insufficiency. Administration of GEMZAR may exacerbate underlying hepatic insufficiency.

The optimum regimen for safe administration of GEMZAR with therapeutic doses of radiation has not yet been determined in all tumor types. GEMZAR has radiosensitizing activity and radiation recall reactions have been reported.

It is not known whether GEMZAR or its metabolites are excreted in human milk.

The effectiveness of GEMZAR in pediatric patients has not been demonstrated.

The toxicities of GEMZAR observed in pediatric patients were similar to those reported in adults.

GEMZAR clearance is affected by age as well as gender.

Patients receiving therapy with GEMZAR should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.

Monitoring and Dosage Modifications
Dosage adjustments for hematologic toxicity may be required.

Serum creatinine, potassium, calcium, and magnesium should be monitored during combination therapy with cisplatin.

Patients should be assessed with a CBC, including differential and platelet count, prior to each dose of GEMZAR. Modify or suspend therapy according to the Dosage Reduction Guidelines in the full Prescribing Information.

Hepatic and renal function (including transaminases and serum creatinine) should be evaluated prior to therapy with GEMZAR and periodically thereafter.

Abbreviated Adverse Events (% incidence)
The most severe adverse events (grades 3/4) with GEMZAR plus cisplatin for the first-line treatment of patients with NSCLC in comparative trials of a 28-day regimen (GEMZAR plus cisplatin versus cisplatin alone) and a 21-day regimen (GEMZAR plus cisplatin versus etoposide plus cisplatin), respectively, were neutropenia (57 vs 4, 64 vs 76); thrombocytopenia (50 vs 4, 55 vs 13); leukopenia (46 vs 3, 29 vs 43); anemia (25 vs 7, 22 vs 15); nausea 28d (27 vs 21); vomiting 28d (23 vs 19); nausea/vomiting 21d (39 vs 26); neuromotor 28d (12 vs 3); hypomagnesemia 28d (7 vs 2); neurohearing 28d (6 vs 6); creatinine elevation 28d (5 vs 3); and dyspnea (7 vs 5, 1 vs 0). The most common adverse events (all grades) of the 28-day regimen (GEMZAR plus cisplatin versus cisplatin alone) and the 21-day regimen (GEMZAR plus cisplatin versus etoposide plus cisplatin), respectively, were anemia (89 vs 67, 88 vs 77); leukopenia (82 vs 25, 86 vs 87); neutropenia (79 vs 20, 88 vs 87), thrombocytopenia (85 vs 13, 81 vs 45), lymphocytopenia 28d (75 vs 51); hematuria (15 vs 13, 22 vs 10); creatinine 28d (38 vs 31), hyperglycemia 28d (30 vs 23); hypomagnesemia 28d (30 vs 17); nausea 28d (93 vs 87); vomiting 28d (78 vs 71); nausea and vomiting 21d (96 vs 86); alopecia (53 vs 33, 77 vs 92); neuromotor 28d (35 vs 15); constipation (28 vs 21, 17 vs 15); neurohearing 28d (25 vs 21); paresthesias 21d (38 vs 16); and infection (18 vs 12, 28 vs 21).

The most severe adverse events (grades 3/4) with GEMZAR plus carboplatin versus carboplatin, respectively, for the treatment of patients with advanced ovarian cancer were neutropenia (71 vs 12), thrombocytopenia (35 vs 11), leukopenia (53 vs 7), anemia (28 vs 11), nausea (6 vs 3), vomiting (6 vs 3), and constipation (7 vs 3). The most common adverse events (all grades) were neutropenia (90 vs 58); leukopenia (86 vs 70); anemia (86 vs 75); and thrombocytopenia (78 vs 57); RBC transfusion (38 vs 15), alopecia (49 vs 17), neuropathy/sensory (29 vs 27), nausea (69 vs 61), fatigue (40 vs 32), vomiting (46 vs 36), diarrhea (25 vs 14), and constipation (42 vs 37).

The most severe adverse events (grades 3/4) with GEMZAR plus paclitaxel versus paclitaxel, respectively, for the treatment of patients with MBC were neutropenia (48 vs 11); alopecia (18 vs 22); leukopenia (11 vs 2); anemia (7 vs 4); fatigue (7 vs 2); thrombocytopenia (6 vs 2); ALT elevation (6 vs 1); and neuropathy-sensory (6 vs 3). The most common adverse events (all grades) were alopecia (90 vs 92); anemia (69 vs 51); neutropenia (69 vs 31); neuropathy-sensory (64 vs 58); nausea (50 vs 31); fatigue (40 vs 28); myalgia (33 vs 33); vomiting (29 vs 15); and thrombocytopenia (26 vs 7).

The most severe adverse events (grades 3/4) with GEMZAR versus 5-FU for the first-line treatment of patients with pancreatic cancer and data reported from a single agent safety database, respectively, were neutropenia (26 vs 5, 24); alkaline phosphatase elevation (16 vs 17, 20); AST elevation (12 vs 2, 17); nausea/vomiting (13 vs 5, 12); ALT elevation (10 vs 0, 11); anemia (10 vs 0, 10); leukopenia (10 vs 2, 9); thrombocytopenia (10 vs 2, 8); bilirubin elevation (4 vs 9, 8); and pain (2 vs 0, 7). The most common adverse events (all grades), defined as reported in > 25% of patients, were AST elevation (72 vs 52, 78); alkaline phosphatase elevation (71 vs 64, 77); anemia (65 vs 45, 73); ALT elevation (72 vs 38, 72); leukopenia (71 vs 15, 64); nausea and vomiting (64 vs 58, 71); neutropenia (62 vs 18, 61); thrombocytopenia (47 vs 15, 36); pain (10 vs 7, 42); fever (30 vs 16, 38); proteinuria (10 vs 2, 32); constipation (10 vs 11, 31); diarrhea (24 vs 31, 30); rash (24 vs 13, 28); and bilirubin elevation (16 vs 25, 26).

See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information for safety and dosing guidelines.

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