2007-06-02

Study Supports Activity of GEMZAR(R) (Gemcitabine HC1 for Injection) in the Treatment of Early-Stage Breast Cancer


Chicago (ots/PRNewswire) -

- Five Phase III Early-Stage Breast Cancer Studies Underway WithGEMZAR

GEMZAR(R) (gemcitabine HC1 for injection), approved in combinationwith paclitaxel (Taxol(R)) in the first-line, post-surgical treatmentof metastatic breast cancer, was the subject of a study presentedtoday with encouraging results in the pre-surgical treatment ofbreast cancer. The study was presented at the 43rd Annual Meeting ofthe American Society of Clinical Oncology (ASCO).

Results showed that adding GEMZAR to the current standard-of-caretreatment was a promising regimen for patients with stage II-IIIbreast cancer. Eli Lilly and Company, the manufacturer and marketerof GEMZAR, also cited five completed or ongoing Phase III trialswhich will further study GEMZAR as a chemotherapeutic foundation forthe treatment of early-stage breast cancer.

Today's Phase II study (Abstract # 595(i)) evaluated the additionof GEMZAR to the current standard-of-care of epirubicin andcyclophosphamide followed by paclitaxel in patients with stage II-IIIbreast cancer. The treatment schedule was a dose-dense sequentialneoadjuvant (pre-surgical) chemotherapy combination, meaning that thecombination was administered at shorter intervals between treatments.Results showed a promising regimen in terms of pathologic completeresponse (pCR-the absence of invasive tumor in the breast). Inaddition, patients who tested positive for the HER-2 gene also weregiven trastuzumab (Herceptin(R)) and demonstrated additionalresponse.

"The data released today reflects our ongoing, aggressive researchplan involving GEMZAR as a key therapeutic foundation for thetreatment of breast cancer," said Allen Melemed, M.D., medicaldirector, global oncology at Lilly. "We are encouraged with theactivity GEMZAR has shown in this breast cancer study."

Enrollment has been completed in one trial, and is ongoing in anadditional four, Phase III early-stage breast cancer studiesevaluating the addition of GEMZAR to commonly-used treatmentregimens. Two adjuvant (post-surgical) therapy trials, NSABP B-38(4,400 patients) and TANGO (3,000 patients), will compare theaddition of GEMZAR to the paclitaxel arm of each study. A thirdadjuvant trial, SUCCESS (3,600 patients), will compare the additionof GEMZAR to a docetaxel-based regimen. Two additional trials, whichare neoadjuvant specific, NSABP B-40 (1,200 patients) and Neo-TANGO(800 patients), will evaluate the addition of GEMZAR to thepaclitaxel or docetaxel arm of the treatment regimen. For moreinformation on these studies, log on to www.lillytrials.com orwww.clinicaltrials.gov.

More About ASCO Abstract # 595

The trial enrolled stage II-III breast cancer patients (with amedian age of 45), including inflammatory tumors, a type of breastcancer that causes the breast to swell, redden and feel warm. Of the73 patients enrolled in the study, 42 (57.5%) were classified as T2;12 (16.5%) as T3, and; 19 (26%) as T4, which included 13 patientswith inflammatory tumors. A T-classification represents the stage ofthe tumor with T4 being the most advanced. A biopsy was performedbefore treatment for the biomarker component of the study.

Patients received a first sequence of epirubicin andcyclophosphamide (90/600 mg/m squared) for three cycles followed by asecond sequence of paclitaxel and GEMZAR (150/2500 mg/m squared) forsix cycles. Treatment was administered on day one, every two weeks,with growth factor support. HER-2 positive patients (20 patients,27.3%), were given trastuzumab (2 mg/kg with a loading dose 4 mg/kg)concomitantly. Afterward, the patients underwent surgery,radiotherapy and adjuvant hormonal therapy according to institutionalpractice.

All patients from the study showed response to the regimen. Of theentire study group, 27 (36.9%) patients achieved a pCR (absence ofinvasive tumor in the breast), with 50% representation from the HER-2positive patients who also were given trastuzumab. Forty-sevenpatients (64.4%) underwent conservative surgery.

The grade 3/4 hematological toxicities were: leukopenia in sixpatients (9%); neutropenia (a decrease in white blood cells) in eightpatients (12%), and; anemia (a decrease in red blood cells) in one(2%). Nausea (13%) and vomiting (15%) were the most frequent grade3/4 non-hematological toxicities. Asymptomatic decrease in cardiacejection fraction was observed in one patient treated withtrastuzumab with subsequent normalization.

About Breast Cancer

Breast cancer is the most common form of cancer among women,affecting nearly one out of every eight women.(ii) The disease isdiagnosed in more than 1.1 million women worldwide each year.(iii)Breast cancer progresses in stages based on tumor size, how thecancer affects the lymph nodes and whether it has metastasized toother parts of the body.(iv) In general, individuals with earlierstages of disease have better chances for long-term survival andrecovery.

GEMZAR

Indications

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

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

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

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

Important Safety Information for GEMZAR

Myelosuppression is usually the dose-limiting toxicity with GEMZARtherapy.

Contraindication

Known hypersensitivity to GEMZAR. Anaphylactoid reaction has beenreported rarely.

Warnings

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

Pulmonary toxicity has been reported with the use of GEMZAR. Incases of severe lung toxicity, GEMZAR therapy should be discontinuedimmediately and appropriate supportive care measures instituted.

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

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

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

Precautions

Use caution in patients with pre-existing renal impairment orhepatic insufficiency. Administration of GEMZAR may exacerbateunderlying hepatic insufficiency.

The optimum regimen for safe administration of GEMZAR withtherapeutic doses of radiation has not yet been determined in alltumor types. GEMZAR has radiosensitizing activity and radiationrecall reactions have been reported.

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

The effectiveness of GEMZAR in pediatric patients has not beendemonstrated.

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

GEMZAR clearance is affected by age as well as gender.

Patients receiving therapy with GEMZAR should be monitored closelyby a physician experienced in the use of cancer chemotherapeuticagents.

Monitoring and Dosage Modifications

Dosage adjustments for hematologic toxicity may be required.

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

Patients should be assessed with a CBC, including differential andplatelet count, prior to each dose of GEMZAR. Modify or suspendtherapy according to the Dosage Reduction Guidelines in the fullPrescribing Information.

Hepatic and renal function (including transaminases and serumcreatinine) should be evaluated prior to therapy with GEMZAR andperiodically thereafter.

Adverse Events

The most severe adverse events (grades 3/4) with GEMZAR pluspaclitaxel for the treatment of patients with MBC were neutropenia(48%); alopecia (18%); leukopenia (11%); anemia (7%); fatigue (7%);thrombocytopenia (6%); ALT elevation (6%); and neuropathy-sensory(6%). The most common adverse events (all grades) were nausea (50%);fatigue (40%); myalgia (33%); and vomiting (29%). The most severeadverse events (grades 3/4) with GEMZAR for the first-line treatmentof patients with pancreatic cancer were neutropenia (24%-26%);alkaline phosphatase elevation (16%-20%); AST elevation (12%-17%);nausea/vomiting (12%-13%); ALT elevation (10%-11%); anemia (10%);leukopenia (9%-10%); thrombocytopenia (8%-10%); bilirubin elevation(4%-8%); and pain (2%-7%). The most common adverse events (allgrades) were AST (72%-78%); alkaline phosphatase (71%-77%); anemia(65%-73%); ALT (72%); leukopenia (64%-71%); nausea and vomiting(64%-71%); neutropenia (61%-62%); thrombocytopenia (36%-47%); pain(10%-42%); fever (30%-38%); proteinuria (10%-32%); constipation(10%-31%); diarrhea (24%-30%); rash (24%-28%); and bilirubin(16%-26%).

The most severe adverse events (grades 3/4) with GEMZAR pluscisplatin for the first-line treatment of patients with NSCLC wereneutropenia (57%-64%); thrombocytopenia (50%-55%); leukopenia(29%-46%); anemia (22%-25%); nausea (27%); vomiting (23%);nausea/vomiting (39%); neuromotor (12%); hypomagnesemia (7%);neurohearing (6%); creatinine elevation (5%); alopecia (1%-13%); anddyspnea (1%-7%). The most common adverse events (all grades) wereparesthesias (38%); hyperglycemia (30%); infection (18%-28%); andconstipation (17%-28%).

The most severe adverse events (grades 3/4) with GEMZAR pluscarboplatin for the treatment of patients with advanced ovariancancer were neutropenia (71%), thrombocytopenia (35%), leukopenia(53%), anemia (28%), nausea (6%), vomiting (6%), and constipation(7%). The most common adverse events (all grades) were RBCtransfusion (38%), alopecia (49%), neuropathy/sensory (29%), nausea(69%), fatigue (40%), vomiting (46%), diarrhea (25%), andconstipation (42%).

See complete Warnings, Precautions, Adverse Reactions, and Dosageand Administration sections in the accompanying full PrescribingInformation for safety and dosing guidelines.

About Lilly Oncology, a Division of Eli Lilly and Company

For more than four decades, Lilly Oncology has been collaboratingwith cancer researchers to deliver innovative treatment choices andvaluable programs to patients and their physicians. Inspired bycourageous patients living with cancer, Lilly Oncology is providingtreatments that are considered global standards of care anddeveloping a broad portfolio of novel targeted therapies toaccelerate the pace and progress of cancer care. To learn more aboutLilly's commitment to cancer, please visit www.LillyOncology.com.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing agrowing portfolio of first-in-class and best-in-class pharmaceuticalproducts by applying the latest research from its own worldwidelaboratories and from collaborations with eminent scientificorganizations. Headquartered in Indianapolis, Ind., Lilly providesanswers - through medicines and information - for some of the world'smost urgent medical needs.

P-LLY

ALIMTA(R) (pemetrexed for injection), Lilly GEMZAR(R) (gemcitabine HCl for injection), Lilly Taxol(R) (paclitaxel), Bristol-Meyers Squibb Herceptin(R) (trastuzumab), Genentech

This press release contains forward-looking statements about thepotential of GEMZAR for the treatment of breast cancer and reflectsLilly's current beliefs. However, as with any pharmaceutical productunder development, there are substantial risks and uncertainties inthe process of development, commercialization, and regulatory review.There is no guarantee that the product will receive additionalregulatory approvals. There is also no guarantee that the productwill continue to be commercially successful. For further discussionof these and other risks and uncertainties, see Lilly's filing withthe United States Securities and Exchange Commission. Lillyundertakes no duty to update forward-looking statements.

(i) Sanchez-Munoz A, Duenos-Garcia R, et al. Neoadjuvantchemotherapy with a dose-dense sequential combination of epirubicinand cyclophosphamide followed by paclitaxel and gemcitabine +/-trastuzumab in stage II and III breast cancer. Correlation betweenpathologic complete response and biologic markers. Abstract #595,American Society of Clinical Oncology (ASCO) Annual Meeting 2007.

(ii) American Cancer Society, "What Are the Key Statistics forBreast Cancer?," American Cancer Society, www.cancer.org, (May 2,2007).

(iii) Pan American Health Organization, "Guidelines forInternational Breast Health and Cancer Control," www.paho.org, (March21, 2006).

(iv) American Cancer Society, "How is Breast Cancer Staged?,"American Cancer Society, www.cancer.org (February 28, 2007).

(Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO)

ots Originaltext: Eli Lilly and CompanyIm Internet recherchierbar: http://www.presseportal.de

Contact:Gregory L. Clarke, Lilly, +1-317-276-5222 (office), +1-317-554-7119 (mobile), gregory.clarke@lilly.com; or Neil Hochman, CPR Worldwide, +1-212-453-2067 (office), +1-516-784-9089 (mobile), n.hochman@cprworldwideusa.com . NewsCom: http://www.newscom.com/cgi-bin/prnh/20070602/CLSA001 , PRN Photo Desk, photodesk@prnewswire.com

Eli Lilly and Company

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Study Supports Activity of GEMZAR(R) (Gemcitabine HC1 for Injection) in the Treatment of Early-Stage Breast Cancer

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