Vinorelbine Tartrate

V

Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: 3?,4?-Didehydro-4?-deoxy-C?-norvincaleukoblastine [R-(R*, R*)]-2,3-dihydroxybutane dioate (1:2)
Molecular Formula: C45H54N4O8•2C4H6O6
Brands: Navelbine

Experience of Supervising Clinician

Use under supervision of a qualified clinician experienced in therapy with antineoplastic agents.b c

Administration Warnings

For IV use only.b c

Fatal if given intrathecally.b c (See Intrathecal Administration under Cautions.)

Extremely important to properly place IV needle or catheter before vinorelbine is injected.b c

Local tissue necrosis and/or thrombophlebitis, if extravasation occurs.b c

Granulocytopenia

Severe granulocytopenia may occur, possibly resulting in increased susceptibility to infection.b c

Granulocyte counts should be ?1000/mm3 prior to administration of vinorelbine.b c

Adjust dosage according to complete blood counts with differentials obtained on day of treatment.b c

Introduction

Antineoplastic agent; semisynthetic vinca alkaloid.1 4 21 b c

Uses for Vinorelbine Tartrate Non-Small Cell Lung Cancer

Used alone or in combination with cisplatin as first-line therapy in ambulatory patients for the palliative treatment of unresectable, advanced non-small cell lung cancer (NSCLC).1 19 91 b c

Used alone or in combination with cisplatin in patients with Stage IV NSCLC.1 19 91 b c

Use in combination with cisplatin is preferred treatment of advanced NSCLC in patients with good performance status because of improved response and survival.1 12 19 99 112

Used in combination with cisplatin in patients with Stage III NSCLC.1 19 91 b c

Use in combination with cisplatin is being investigated for adjuvant treatment of completely resected NSCLC†.110 111

Breast Cancer

Use in combination with trastuzumab is being investigated for the treatment of HER2-overexpressing metastatic breast cancer†.19 104 105 106

Has been used as first-line or salvage therapy for metastatic breast cancer in combination with various other agents†, including anthracyclines (e.g., doxorubicin), fluoropyrimidines (e.g., fluorouracil, capecitabine), mitoxantrone, cisplatin, taxanes (e.g., docetaxel, paclitaxel), ifosfamide, or gemcitabine.122

Has been used as monotherapy in first-line or salvage (e.g., second-line or subsequent) treatment of metastatic breast cancer†.19 106

Cervical Cancer

Use in the treatment of metastatic or recurrent cervical cancer† is being investigated.19 97 98

Use in combination with other antineoplastic agents (e.g., cisplatin) is being evaluated in patients with metastatic or recurrent cervical cancer†.98

Adult Soft Tissue Sarcomas

Has been used in the treatment of adult soft tissue sarcomas†.19

Esophageal Cancer

Has been used in the treatment of esophageal cancer†.19

Vinorelbine Tartrate Dosage and Administration General

Consult specialized references for procedures for proper handling and disposal of antineoplastics.1 b c

Handle drug with caution and avoid exposure (e.g., use gloves) during handling and preparation of IV solution.1 b c If skin or mucosal contact occurs, immediately and thoroughly wash skin or mucosa with soap and water.1 b c

Avoid contact of the drug with the eyes since severe irritation may occur; immediately wash eyes thoroughly with water. 1 b c

Administration IV Administration

For solution and drug compatibilty information, see Compatibility under Stability.

Administer IV only by individuals experienced in the administration of the drug.b c

Very irritating; do not administer IM, sub-Q, or intrathecally.1 b c Intrathecal administration of other vinca alkaloids has resulted in death.1 b c (See Boxed Warning.)

Management of patients mistakenly receiving intrathecal vinorelbine is a medical emergency.b c (See Intrathecal Administration under Cautions.)

Administer by IV injection, usually at weekly intervals.1 b c Inject the diluted injection concentrate into a free-flowing IV infusion or a large central vein.1 3 9 20

Has been administered as a continuous IV infusion†.44 72 73

Extravasation

Extremely important to ensure that needle or catheter is securely within vein to avoid extravasation.1 b c If extravasation occurs, discontinue injection immediately and administer remainder of dose through another vein.1 b c

Dilution

Dilute injection concentrate prior to injection in a syringe with 5% dextrose injection or 0.9% sodium chloride injection to a final vinorelbine concentration of 1.5–3 mg/mL or in an IV bag with 5% dextrose injection, 0.9% sodium chloride injection, 0.45% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection, Ringer’s injection, or lactated Ringer’s injection to a final vinorelbine concentration of 0.5–2 mg/mL.1 b c

Rate of Administration

Administer over 6–10 minutes into the side port closest to the IV bag of a free-flowing IV infusion or into a large central vein.1 3 9 Follow by flushing with at least 75–125 mL of 0.9% sodium chloride injection or 5% dextrose injection over a period of 10 minutes.1 3 9 73 b c

Dispensing Precautions

When dispensing, must label syringe holding the individual dose with the statement: “Warning: For IV use only. Fatal if given intrathecally.”1 b c

Dosage

Available as vinorelbine tartrate; dosage expressed in terms of vinorelbine.1 b c

Adults Non-small Cell Lung Cancer Monotherapy IV

Initially, 30 mg/m2 once weekly until disease progression or dose-limiting toxicity occurs.1 b

Combination Therapy IV

Vinorelbine 25 mg/m2 once weekly in combination with cisplatin 100 mg/m2 every 4 weeks.1 b

Alternatively, vinorelbine 30 mg/m2 once weekly in combination with cisplatin (120 mg/m2 on days 1 and 29 and then once every 6 weeks).1 b

Breast Cancer† First-line or Salvage (second-line or subsequent) Monotherapy IV

Initially, 20–30 mg/m2 (infused over 20–60 minutes) weekly.3 5 9 20 21 22 23 24 25 26 27 28 30 31 32 33 34 35

Alternatively, 30 mg/m2 weekly as a direct IV injection over 3–5 minutes30 or as a rapid IV dose.3 20 34 However, manufacturers recommend to infuse over 6–10 minutes to improve local tolerance.73 b c

Adjust doses (e.g., delay or reduce doses) throughout therapy to minimize potential toxicity.3 5 20 21 22 23 24 25 27 28 30 31 32 33 34 35 52

Dosage Modification for Toxicity Hematologic Toxicity

Granulocyte counts should be ?1000/mm3 prior to administration.b c

Perform CBC with differential before administration of each dose; consider withholding next dose in patients with granulocytopenia or infectious complications.b c

Adjust dosage according to hematologic toxicity.b c

Table 1. Dosage Adjustments Based on Granulocyte Counts1bc

Granulocytes on Day of Treatment (cells/mm3)

Percentage of Starting Dose of Vinorelbine

?1500

100%

1000 to 1499

50%

<1000

Do not administer. Repeat granulocyte count in 1 week. If 3 consecutive weekly doses are held because granulocyte count is <1,000/mm3, discontinue drug.

Table 2. Dosage Adjustments Based on Granulocyte Counts. If fever and/or sepsis is present while granulocytopenic or 2 consecutive weekly dosages held due to granulocytopenia, reduce subsequent dosages by the following:1b

Granulocytes on Day of Treatment (cells/mm3)

Percentage of Starting Dose of Vinorelbine

?1500

75%

1000 to 1499

37.5%

<1000

Do not administer. Repeat granulocyte count in 1 week. If 3 consecutive weekly doses are held because granulocyte count is <1,000/mm3, discontinue drug.

Hepatic Toxicity

Adjust dosage according to hepatic toxicity.b c

Reduce dosage in patients who develop hyperbilirubinemia based on total bilirubin levels.1 b c

Adjust dosage to lower end of dosage range for patients with concurrent hepatic impairment and hematologic toxicity.1 b c

Table 3. Dose Modification Based on Total Bilirubin1bc

Total Bilirubin (mg/dL)

Percentage of Starting Dose of Vinorelbine

?2

100%

2.1 to 3

50%

>3

25%

Neurologic Toxicity

If manifestations of moderate or severe (grade 2 or higher) neurotoxicity occur, discontinue therapy immediately.1 b c

Prescribing Limits Adults Non-small Cell Lung Cancer IV

Stage III NSCLC: Maximum 4 cycles of chemotherapy.99

Stage IV NSCLC: Maximum 4 cycles if disease not responding to treatment; maximum 6 cycles of chemotherapy if disease responds to treatment.99

Special Populations Hepatic Impairment

Adjust dosage to lower end of dosage range for patients with concurrent hepatic impairment and hematologic toxicity.1 b c

Reduce dosage in patients who develop hyperbilirubinemia.1 b c (See Hepatic Toxicity under Dosage and Administration.)

Renal Impairment

No dosage adjustments required in patients with renal impairment.1 b c

Cautions for Vinorelbine Tartrate Contraindications

Patients with pretreatment granulocyte counts <1000/mm3.1 b c

Warnings/Precautions Warnings Intrathecal Administration

Fatal if administered intrathecally; management of patients mistakenly receiving intrathecal vinorelbine is a medical emergency.1 73

Prognosis to date for patients inadvertently receiving another vinca alkaloid generally has been poor despite immediate efforts to remove spinal fluid and flush with lactated Ringer’s injection and other solutions, with such efforts failing to prevent ascending paralysis and death in almost all cases.93 94

In one adult patient, progression of paralysis was stopped when treatment was initiated immediately after inadvertent intrathecal injection of vincristine.93

Treatment consisted of immediate removal of as much CSF as safely possible via lumbar access, followed by flushing of the subarachnoid space with lactated Ringer’s solution infused continuously at a rate of 150 mL/hour through a catheter in a cerebral lateral ventricle and removal of fluid through a lumbar access.93

As soon as available, fresh frozen plasma (25 mL) diluted in 1 L of lactated Ringer’s solution was infused through the cerebral ventricular catheter at a rate of 75 mL/hour with removal of fluid through the lumbar access.93 The rate of infusion was adjusted to maintain a CSF protein concentration of 150 mg/dL.93 Glutamic acid was administered in a dose of 10 g given IV over 24 hours, followed by 500 mg orally 3 times daily for 1 month or until stabilization of neurologic status.93 94 The role of glutamic acid in this treatment is uncertain.93

Hematologic Effects

Granulocytopenia usually is the dose-limiting factor in therapy.b c Nadir in granulocyte count generally occurs 7–10 days after administration and recovery usually occurs within another 7–14 days.1 5 21 23 26 b c

Perform CBC with differential before administration of each dose.b c

Do not administer if granulocyte counts <1000/mm3.b c

Carefully monitor patients with severe granulocytopenia for evidence of infection and/or fever.b c (See Hematologic Toxicity under Dosage and Administration.)

Respiratory Effects

Acute shortness of breath and severe bronchospasm have occurred rarely; most frequently when mitomycin was administered concomitantly.1 b c May require treatment with supplemental oxygen, bronchodilators, and/or corticosteroids, particularly with preexisting pulmonary dysfunction.b c

Fatal interstitial pulmonary changes and acute respiratory distress syndrome (ARDS) have been reported.1 b c Mean time to onset of symptoms was 1 week (range: 3–8 days).b c Evaluate promptly patients with preexisting pulmonary dysfunction or new onset of dyspnea, cough, hypoxia, or other symptoms.b c

GI Effects

GI effects (some fatal), including severe constipation (grade 3 or 4), paralytic ileus, intestinal obstruction, necrosis, and/or perforation reported.b c

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.1 b c Avoid pregnancy during therapy.1 b c If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.1 b c

Major Toxicities Hepatic Toxicity

Adjust dosage according to hepatic toxicity.b c (See Hepatic Toxicity under Dosage and Administration.)

General Precautions

Administer only under constant supervision by clinicians experienced in therapy with chemotherapeutic agents.1 b c

Pattern of adverse effects appears to be similar in patients receiving monotherapy or combination therapy with vinorelbine.1 b c

Most drug-related adverse effects are reversible.b c If severe adverse effects occur, reduce dosage or discontinue therapy.b c Reinstitute therapy with caution; possible recurrence of toxicity.b c

Compromised Bone Marrow Reserve

Use with extreme caution in patients whose bone marrow reserve may have been compromised by prior chemotherapy or radiation therapy, or whose marrow function is recovering from previous cytotoxic therapy.b c

Nervous System Effects

Monitor patients with preexisting neuropathy, regardless of etiology, for new or worsening signs and symptoms, while receiving the drug.b c

Eye Contamination

Avoid contamination of the eye(s) with the drug; severe irritation may occur with accidental exposure.b c If contamination occurs, immediately wash eye(s) with water.b c

Hepatic Effects

Transient elevations of liver enzymes were reported without clinical symptoms.1 21 26 80 (See Hepatic Toxicity under Dosage and Administration.)

Specific Populations Pregnancy

Category D.c (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether vinorelbine is distributed into milk.1 b c Discontinue nursing or drug.1 b c

Pediatric Use

Safety and efficacy in children <18 years of age have not been established.1 20 b c

Limited number of pediatric patients with recurrent solid malignant tumors (e.g., rhabdomyosarcoma/undifferentiated sarcoma, neuroblastoma, CNS tumors) have received vinorelbine dosages similar to adults; no clinical efficacy reported.b c Toxicities were similar to adults.b c

Geriatric Use

No overall differences in safety and efficacy relative to younger adults.1 b c Although response in patients ?65 years of age does not appear to differ from that in younger adults, possibility exists of greater sensitivity in some geriatric patients.1 b c

Hepatic Impairment

No evidence that vinorelbine-associated toxicity is increased in patients with elevated hepatic enzymes.b c

Administer with caution and reduce dosage in patients with severe hepatic impairment, since drug is metabolized by hepatic enzymes and clinical experience in severe hepatic impairment is limited.b c (See Hepatic Toxicity under Dosage and Administration.)

Renal Impairment

Dosage reduction in patients with renal impairment does not appear to be necessary.1 b c

Common Adverse Effects

Myelosuppression, anemia, injection site reactions (e.g., erythema, pain, chemical phlebitis, vein discoloration), fatigue, chest pain, constipation, nausea, vomiting, hypertension, malaise, paresthesia, peripheral neuropathy, loss of deep tendon reflexes, diarrhea, asthenia.1 b c

Interactions for Vinorelbine Tartrate Drugs Affecting Hepatic Microsomal Enzymes

Metabolized by CYP isoenzymes, principally CYP3A.1 b c

Inhibitors of CYP3A: Potential pharmacokinetic interaction (inhibition of vinorelbine metabolism). 1 b Use concomitantly with caution.1 b c

Ototoxic Drugs

Since varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage have been reported in patients receiving vinca alkaloids, use concomitantly with other potentially ototoxic drugs with extreme caution.1 93 (See Specific Drugs under Interactions.)

Specific Drugs and Procedures

Drug

Interaction

Comments

Aprepitant

May inhibit or induce CYP3A4103

Use concomitantly with caution and careful monitoring103

Consider dosage reduction of vinorelbine 103

Cisplatin

Incidence of of granulocytopenia increased with combined use1 b c

Closely monitor CBC with differentials before, during and after therapy1 b c

Itraconazole

Possible increased plasma concentrations of vinorelbine102

Possible neurotoxicity; consider vinorelbine dosage reduction102

Use with caution, earlier onset and/or increased severity of adverse effects may occur1 b c

Ketoconazole

Possible increased plasma concentrations of vinorelbine102

Possible neurotoxicity; consider vinorelbine dosage reduction102

Use with caution, earlier onset and/or increased severity of adverse effects may occur1 b c

Mitomycin

Possible acute pulmonary reactions 1 b (See Respiratory Effects under Cautions)

Ototoxic drugs (e.g., platinum-containing antineoplastic agents)

Potential additive ototoxic effect1 93

Varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage use with extreme caution1 93

Paclitaxel

Possible increased risk of neuropathy1

Monitor for signs and symptoms of neuropathy1 b c

Radiation Therapy

Prior or concomitant radiation may result in radiosensitizing effectsb c

Voriconazole

Possible increased plasma concentrations of vinorelbine102

Possible neurotoxicity; consider vinorelbine dosage reduction102

Use with caution, earlier onset and/or increased severity of adverse effects may occur1 b c

Vinorelbine Tartrate Pharmacokinetics Absorption Plasma Concentrations

Following IV administration, plasma concentrations decline in a triphasic manner with an initial rapid decrease.1 b c

Distribution Extent

Distributed into peripheral compartments.1 b c

Crosses the placenta in animals; not known if crosses the placenta in humans.b c

Not known whether vinorelbine is distributed into human milk.1 b c

Plasma Binding

High degree (79.6–91.2% in cancer patients) of binding to human platelets and lymphocytes.1 b c

Elimination Metabolism

Extensively metabolized, mainly in the liver by CYP3A isoenzymes to vinorelbine N-oxide and deacetylvinorelbine (main metabolite with antitumor activity similar to the parent drug).1 b c

Elimination Route

Excreted, mainly as unchanged drug, in urine (11–18%) and in feces (46%).1 b c

Half-life

Mean terminal elimination half-life: 27.7–43.6 hours.1 b c

Special Populations

Effect of renal and/or hepatic impairment on the elimination of vinorelbine not evaluated.1

Metabolism by CYP3A isoenzymes may be impaired in patients with hepatic impairment.b c

Limited data indicate that disposition of drug in geriatric patients is similar to that in younger adults.1 b c

Stability Storage Parenteral Injection

2–8°C; do not freeze.1 b c ; protect from light.1 b c

Unopened vials stable at 25°C for up to 72 hours.1 b c

May store diluted solutions at normal room light (in polypropylene syringes or polyvinyl chloride bags) at 5–30°C up to 24 hours.b c

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral Solution Compatibilityb c HID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aztreonam

Bleomycin sulfate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Carboplatin

Carmustine

Cefotaxime sodium

Ceftazidime

Ceftizoxime sodium

Chlorpromazine HCl

Cimetidine HCl

Cisplatin

Clindamycin phosphate

Cyclophosphamide

Cytarabine

Dacarbazine

Dactinomycin

Daunorubicin HCl

Dexamethasone sodium phosphate

Diphenhydramine HCl

Doxorubicin HCl

Doxorubicin HCl liposome injection

Doxycycline hyclate

Droperidol

Enalaprilat

Etoposide

Famotidine

Filgrastim

Floxuridine

Fluconazole

Fludarabine phosphate

Gallium nitrate

Gatifloxacin

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Hydrocortisone sodium phosphate

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Idarubicin HCl

Ifosfamide

Imipenem–cilastatin sodium

Lorazepam

Mannitol

Melphalan HCl

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Metronidazole

Mitoxantrone HCl

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Oxaliplatin

Potassium chloride

Prochlorperazine edisylate

Promethazine HCl

Rantidine HCl

Streptozocin

Teniposide

Ticarcillin disodium–clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Zidovudine

Incompatible

Acyclovir sodium

Allopurinol sodium

Aminophylline

Amphotericin B

Amphotericin B cholesteryl sulfate complex

Ampicillin sodium

Cefazolin sodium

Cefotetan disodium

Ceftriaxone sodium

Cefuroxime sodium

Co-trimoxazole

Fluorouracil

Furosemide

Ganciclovir sodium

Lansoprazole

Methylprednisolone sodium succinate

Mitomycin

Sodium bicarbonate

Thiotepa

Variable

Heparin sodium

ActionsActions

Mechanism of action not fully elucidated; vinorelbine and other vinca alkaloids exert their cytotoxic effects by binding to tubulin, the protein subunit of the microtubules that form the mitotic spindle.3 5 6 7 8 9 10 21

Formation of vinorelbine-tubulin complexes prevents the polymerization of the tubulin subunits into microtubules, induces depolymerization of microtubules resulting in inhibition of microtubule assembly and cellular metaphase arrest.1 3 5 6 7 8 9 10 21

Also interferes with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent calcium2 +-transport ATPase activity, cellular respiration; and nucleic acid and lipid biosynthesis.1 21 b c

Advice to Patients

Importance of advising patients about hematologic toxicity and increased risk of infection.b c

Importance of immediately informing clinician if fever or chills occur.b c

Importance of informing clinician if increased shortness of breath, cough, or other new pulmonary symptoms occur.1 b

Importance of informing clinician if abdominal pain or constipation occurs.1 b c

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 b c

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 b c Advise patients to avoid becoming pregnant during treatment.b c

Importance of informing patients of other important precautionary information.b c (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Vinorelbine Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion only

10 mg (of vinorelbine)/mL (10 and 50 mg)

Navelbine

Pierre Fabre

Vinorelbine Tartrate for Injection

American Pharmaceutical Partners, Baxter, Bedford, Mayne, Sicor

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions December 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. GlaxoSmithKline. Navelbine (vinorelbine tartrate) injection prescribing information. Research Triangle Park, NC; 2002 Nov.

2. Glaxo Wellcome Inc. Treatment IND protocol: Treatment IND for patients with unresectable stage III or IV NSLC and product information. Research Triangle Park, NC: 1994 Mar.

3. Glaxo Wellcome Inc. Navelbine injection product information. Research Triangle Park, NC: 1994 Mar.

4. Xiao-Jian Z, Rahmani R. Preclinical and clinical pharmacology of vinca alkaloids. Drugs. 1992; 44(Suppl 4):1-16. [PubMed 1283846]

5. Cvitkovic E, Izzo J. The current and future place of vinorelbine in cancer therapy. Drugs. 1992; 44(Suppl 4):36-45. [PubMed 1283849]

6. Fellous A. Biochemical effects of navelbine on tubulin and associated proteins. Semin Oncol. 1989;16(Suppl 4):9-14.

7. Binet S. In situ analysis of the action of navelbine on various types of microtubules using immunofluorescence. Semin Oncol. 1989; 16(Suppl 4):5-8. [PubMed 2652320]

8. Binet S. Immunofluorescence study of the action of navelbine, vincristine and vinblastine on mitotic and axonal microtubules. Int J Cancer. 1990; 46:262-6. [PubMed 2200754]

9. Goa KL, Faulds F. Vinorelbine a review of its pharmacological properties and clinical use in cancer chemotherapy. Drugs Aging. 1994; 5:200-34. [PubMed 7803948]

10. Budman DR. New vinca alkaloids and related compounds. Semin Oncol. 1992; 19:639-45. [PubMed 1462165]

11. Depierre A, Chastang C, Quoix E et al. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994; 5:37-42. [PubMed 8172790]

12. Le Chevalier T, Brisgand D, Douillard J et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: Results of a European multicenter trial including 612 patients. J Clin Oncol. 1994; 12:360-67. [IDIS 326016] [PubMed 8113844]

13. Burroughs Wellcome Company, Research Triangle Park, NC: Personal communication.

14. Horwitz SB. Mechanism of action of taxol. Trends Pharmacol Sci. 1992; 13:134-6. [PubMed 1350385]

15. Rowinsky EK, Cazenave LA, Donehower RC. Taxol: a novel investigational antimicrotubule agent. Natl Cancer Inst. 1990; 82:1247-59.

16. Gregory RE, DeLisa AF. Paclitaxel: a new antineoplastic agent for refractory ovarian cancer. Clin Pharm. 1993; 12:401-15. [IDIS 314324] [PubMed 7691462]

17. Hepperle M, Georg G. Taxol analogs. Drugs Future. 1994; 19:573-84.

18. Balbiani L, Coppola F, Blajman C et al. Navelbine (NVB) vs NVB plus cisplatin (P) in non-small cell lung cancer (NSCLC). Proc Annu Meet Am Soc Clin Oncol. 1993; 12:A1185.

19. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]

20. Burroughs Wellcome, Research Triangle Park, NC: Personal communication.

21. Toso C, Lindley C. Vinorelbine: a novel vinca alkaloid.

Vinorelbine Tartrate

.