Vinblastine (Velban) is a chemotherapeutic drug that belongs to the class of medicines called vinca alkaloids. It arrests the growth of tumor cells and is cell cycle-specific.

Indications of Vinblastine:

• Hodgkin Lymphoma:

  • It is indicated for the treatment of Hodgkin lymphoma.

• Kaposi sarcoma:

  • It is used for the treatment of Kaposi sarcoma.

• Langerhans cell histiocytosis:

  • It is effective in the treatment of histiocytosis X (Letterer-Siwe disease)

• Non-Hodgkin lymphomas:

  • Treatment of lymphocytic lymphoma, histiocytic lymphoma, and advanced mycosis fungoides can be done by vinblastine.

• Testicular cancer:

  • It is helpful in treating testicular malignancy.
  • Has also been used in the treatment of resistant choriocarcinoma.

• Off Label Use of Vinblastine in Adults:

  • Bladder cancer; Kaposi sarcoma, oral lesions (intralesional);
  • Metastatic Melanoma;
  • Non-small cell lung cancer (NSCLC);
  • Advanced Soft tissue sarcoma (desmoid tumors, aggressive fibromatosis)

Vinblastine dose in adults:

Note:

• For IV use only;
• fatal if administered by other routes.
• The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a minibag (NOT a syringe).

Vinblastine Treatment dose of Bladder cancer (off-label): 

• Metastatic disease:

  • Dose-dense MVAC regimen:

    • 3 mg/m² intravenous on day 2 every 14 days (in combination with methotrexate, doxorubicin, cisplatin, and filgrastim) until disease progression or unacceptable toxicity.

  • MVAC regimen:

    • 3 mg/m² intravenous on days 2, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, and cisplatin) for up to 6 cycles or
    • 3 mg/m² intravenous on days 2, 15, and 22 every 28 days (in combination with  methotrexate, doxorubicin, and cisplatin) until disease progression or unacceptable toxicity or
    • 3 mg/m² intravenous on days 1, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, cisplatin, and filgrastim) for up to 6 cycles.

• Neoadjuvant treatment:

  • MVAC regimen:

    • 3 mg/m² intravenous on days 2, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, and cisplatin) for 3 cycles.

  • CMV regimen:

    • 4 mg/m² intravenous on days 1 and 8 every 21 days (in combination with  methotrexate, cisplatin, and leucovorin) for 3 cycles.

Vinblastine Treatment dose of Hodgkin lymphoma (off-label dosing):

• ABVD regimen:

  • Favorable/early-stage disease:

    • 6 mg/m² intravenous on days 1 and 15 of a 28-day cycle (in combination with doxorubicin, bleomycin, dacarbazine, and radiation therapy) for 2 cycles.

  • Unfavorable/early-stage disease:

    • 6 mg/m² intravenous on days 1 and 15 of a 28-day cycle (in combination with doxorubicin, bleomycin, dacarbazine, and radiation therapy) for 4 cycles.

  • Unfavorable/advanced stage disease:

    • 6 mg/m² intravenous on days 1 and 15 of a 28-day cycle (in combination with doxorubicin, bleomycin, dacarbazine, and radiation therapy) for 6 to 8 cycles.

• Stanford V regimen:

  • Favorable/early-stage disease:

    • 6 mg/m² intravenous in weeks 1, 3, 5, and 7 (in combination with doxorubicin, mechlorethamine, vincristine, bleomycin, etoposide, prednisone, and radiation therapy).

  • Unfavorable/advanced stage disease:

    • 6 mg/m² intravenous in weeks 1, 3, 5, 7, 9, and 11 (in combination with doxorubicin, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone).

• VEPEMB regimen:

  • Adults ≥60 years of age:
    • 6 mg/m² intravenous on day 1 of each 28-day cycle (in combination with cyclophosphamide, prednisone/prednisolone, procarbazine, etoposide, mitoxantrone, and bleomycin, ± radiation therapy) for 3 cycles (stage 1A or IIA disease) or for 6 cycles (stage IIB, III, or IV disease).

Vinblastine Treatment dose of Kaposi sarcoma, oral lesions (off-label route; based on limited data):

• • Intralesional:
  • 0.1m per 0.5 cm² lesions injected directly into the lesion (a 0.2 mg/mL vinblastine solution was used).
  • Larger lesions may require multiple injections;
  • The reported range of volume injected: 0.8 to 4 mL.

Vinblastine Treatment dose of Metastatic Melanoma (off-label): 

• CVD + immunotherapy regimen:

  • 5 mg/m² on days 1 to 4 and 22 to 25 of a 6-week treatment cycle (in combination with cisplatin, dacarbazine, aldesleukin, and interferon alfa-2b); may repeat if tumor response.

Vinblastine Treatment dose of Non-small cell lung cancer (off-label): 

• Adjuvant treatment after complete resection:

  • 4 mg/m² I/V on days 1, 8, 15, 22, and 29, then every 2 weeks (in combination with cisplatin) until the last cisplatin dose.

• Concurrent radiation:

  • 5 mg/m² I/V on days 1, 8, 15, 22, and 29 (in combination with cisplatin and concurrent radiation therapy).

Vinblastine Treatment dose of advanced Soft tissue sarcoma (desmoid tumors, aggressive fibromatosis) (off-label):

• • 6 mg/m² Intravenous every 7 to 10 days (dose usually rounded to 10 mg) in combination with methotrexate for 1 year.

Vinblastine Treatment dose of Testicular cancer (off-label dosing):

• VeIP regimen:

  • 11 mg/kg intravenous daily for 2 days every 21 days (in combination with ifosfamide, cisplatin, and mesna) for 4 cycles.

  • Manufacturer's labeling:

    • Hodgkin lymphoma, non-Hodgkin lymphomas (lymphocytic lymphoma, histiocytic lymphoma, advanced mycosis fungoides), testicular cancer, Kaposi sarcoma, Langerhans cell histiocytosis (histiocytosis X, Letterer-Siwe disease):
      • Dosing in the prescribing information may not reflect current clinical practice.
      • 3.7 mg/m² intravenous ;
      • adjust dose every 7 days (based on white blood cell response) up to 5.5 mg/m² (second dose);
      • 7.4 mg/m² (third dose);
      • 9.25 mg/m² (fourth dose); and
      • 11.1 mg/m² (fifth dose).
    • The dose should not be administered more frequently than every 7 days.
    • Usual dosage range: 5.5 to 7.4 mg/m² every 7 days.
    • Maximum dose: 18.5 mg/m²; dosage adjustment goal is to reduce white blood cell count to 3,000/mm³.
    • The frequency and duration of therapy may vary by indication, concomitant combination chemotherapy, and hematologic response.

Vinblastine dose in children:

Note:

• Dosing and frequency depend on the indication, protocol, and/or treatment phase and hematologic response;
• refer to the specific protocol. It can be given intravenous only.
• The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a mini bag (NOT a syringe) to prevent inadvertent intrathecal administration.

Vinblastine Treatment dose of Hodgkin lymphoma:

• Infants, Children, and Adolescents:

  • Manufacturer's labeling:

    • Initial dose: 6 mg/m² /dose I/V, do not administer more frequently than every 7 days.

  • ABVD regimen:

    • 6 mg/m² /dose I/V administered on days 1 and 15 of a 28 day cycle in combination with doxorubicin, bleomycin, and dacarbazine.

  • ChlVPP regimen:

    • 6 mg/m²/dose I/V administered on days 1 and 8 of a 28 day cycle in combination with chlorambucil, procarbazine, and prednisolone;
    • The minimum reported age: 7 months.

Vinblastine Treatment dose of Multisystem Langerhans cell histiocytosis (Letterer-Siwe disease; Histiocytosis X):

• Infants, Children, and Adolescents:

  • Manufacturer's labeling:

    • Initial dose: 6.5 mg/m² /dose I/V; do not administer more frequently than every 7 days

  • Alternate dosing: Limited data available:

    • Induction: 6 mg/m² /dose I/V every 7 days in combination with prednisone for 6 to 12 weeks depending upon clinical response; then begin maintenance therapy of 6 mg/m /dose every 3 weeks in combination with prednisone, continue for a total duration of vinblastine therapy of 12 months.

Vinblastine Treatment dose of Extracranial Germ cell tumors (eg, testicular, ovarian, mediastinal):

• Infants, Children, and Adolescents:

  • Initial dose: 3 mg/m² /dose intravenous; per the manufacturer, do not administer more frequently than every 7 days; however, in some trials, a single dose was used and others used a daily dose of vinblastine administered over 1 hour for 2 days.

Dose in pregnancy and lactation:

• Vinblastine can cross the placenta.
• Guidelines for treatment and follow-up for cancer in pregnancy have been published by the European Society for Medical Oncology.
• The ESMO guidelines recommend that you refer to a hospital with expertise in the treatment of cancer during pregnancy.
• They also encourage a multidisciplinary team (obstetrician/neonatalian, oncology team).
• The first trimester should not receive chemotherapy. It should be withheld after 33 weeks.
• There should also be a three-week period between the last dose of chemotherapy and the expected delivery.
• Guidelines for treatment of hematologic malignancies in pregnancy have been published by an international consensus panel. 
• Vinblastine, which is part of the ABVD regimen is used to treat Hodgkin lymphoma. ABVD can be safely administered in the second stage of pregnancy for early-stage Hodgkin Lymphoma.
• ABVD may be administered in the second or third trimester to patients with advanced-stage diseases.
• Vinblastine treatment should not be used if you are pregnant. Combination therapy with vinblastine can cause reversible amenorrhea.
• Vinblastine therapy can cause permia in males.

Use of vinblastine during breastfeeding

• It is unknown if breast milk secretes vinblastine.
• Comparing to healthy untreated women, the ABVD regimen caused changes in breast milk's bacterial and metabolic compositions. 
• This regimen may make it difficult for women to breastfeed after giving birth if they are pregnant.
• Consider the possibility of serious adverse reactions in breastfed infants.
• The decision to stop taking vinblastine or stop breastfeeding should be made based on the importance to the mother.

Dose adjustment in renal disease:

• No dosage adjustment is necessary.

Vinblastine Dose adjustment in liver disease:

The manufacturer's labeling recommends the following adjustment:

• Serum bilirubin >3 mg/dl:

  • A 50% dose reduction is required.

• The following adjustments have also been recommended:

  • Serum bilirubin 1.5 to 3 mg/dL or transaminases 2 to 3 times ULN:
    • 50% dose reduction is needed.
  • Serum bilirubin >3 times ULN:
    • Use is not recommended.

Side effects of Vinblastine:

• Cardiovascular:

  • Angina Pectoris
  • Cerebrovascular Accident
  • ECG Abnormality
  • Hypertension
  • Ischemic Heart Disease
  • Limb Ischemia
  • Myocardial Infarction
  • Raynaud's Phenomenon

• Central Nervous System:

  • Decreased Deep Tendon Reflex
  • Depression
  • Dizziness
  • Headache
  • Malaise
  • Metallic Taste
  • Neurotoxicity
  • Paresthesia
  • Peripheral Neuritis
  • Seizure
  • Tumor Pain
  • Vertigo

• Dermatologic:

  • Alopecia
  • Dermatitis
  • Skin Blister
  • Skin Photosensitivity
  • Skin Rash

• Endocrine & Metabolic:

  • Hyperuricemia
  • SIADH

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Constipation
  • Diarrhea
  • Enterocolitis
  • Gastrointestinal Hemorrhage
  • Intestinal Obstruction
  • Nausea
  • Paralytic Ileus
  • Stomatitis
  • Toxic Megacolon
  • Vomiting

• Genitourinary:

  • Azoospermia
  • Urinary Retention

• Hematologic & Oncologic:

  • Anemia
  • Bone Marrow Depression
  • Granulocytopenia
  • Hemolytic Uremic Syndrome
  • Leukopenia
  • Rectal Hemorrhage
  • Thrombocytopenia
  • Thrombotic Thrombocytopenic Purpura

• Local:

  • Local Irritation

• Neuromuscular & Skeletal:

  • Jaw Pain
  • Myalgia
  • Ostealgia
  • Weakness

• Ophthalmic:

  • Nystagmus

• Otic:

  • Auditory Disturbance
  • Deafness
  • Vestibular Disturbance

• Respiratory:

  • Bronchospasm
  • Dyspnea
  • Pharyngitis

• Miscellaneous:

  • Radiation Recall Phenomenon

Contraindications to Vinblastine:

• Bacterial infection
• Significant granulocytopenia

Canadian labeling: Additional contraindications that are not found in the US labeling

• Pregnancy
• There is not much evidence of cross-reactivity between drugs within this class and allergenic substances. 
• Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic activities.

Warnings and precautions

• Suppression of bone marrow

  • You can usually see bone marrow suppression, including leukopenia or granulocytopenia, within five to ten days of administration.
  • The recovery process takes 2 weeks, or more.
  • If WBC is less than 2,000/mm, monitor for infection.
  • Leukopenia can be more severe in patients with cachectic conditions and skin ulceration than it is milder when taken at lower doses.
  • Therapy should be stopped if the marrow becomes infected with malignant cells. Anemia is rare.

• Extravasation: [US Boxed Warning]

  • Vinblastine can be used as a vesicant. To avoid extravasation, it is important to place the catheter or needle correctly before and during infusion.
  • Extravasation can cause severe irritation. Vinblastine should only be administered by trained personnel.
  • Extravasation should be treated immediately. Hyaluronidase injections and heat should be administered to the affected areas.
  • To complete the administration, a separate vein should also be used.

• Gastrointestinal toxicities:

  • Stomatitis can be treated with therapy, which is often reversible.

• Neurotoxicity:

  • Vinblastine is known for its neurotoxicity, which can be reversed. 
  • Seizures and severe CNS damage can be caused by higher doses or more frequent use.

• Toxicity in the lungs:

  • Combination therapy with mitomycin may result in severe bronchospasm and acute dyspnoea within minutes to several hours following vinblastine therapy, or up to 14-days after mitomycin administration.
  • It should not be used in patients suffering from preexisting pulmonary diseases.

• Hepatic impairment

  • Vinblastine can cause increased toxicity in patients with hepatic impairment. Therefore, dose adjustment is necessary.

• Ischemic heart disease

  • Vinblastine should not be given to patients suffering from ischemic heart disease.

Vinblastine: Drug Interaction

Monitoring parameters:

• CBC with differential and platelet count
• LFTs
• serum uric acid.

How to administer Vinblastine?

• You should only give it intravenously. It is fatal to try other routes.
• The Institute for Safe Medication Practices recommends that vinblastine be administered in a small bag, and not in a syringe.
• It is preferable to infuse the liquid in a mini bag of 25-50 mL.
• Extended administration times (>=30-60 minutes) and/or higher administration volumes increase the risk of vein irritation or extravasation.

Vesicant

• To avoid extravasation, it is important to properly place the needles or catheters before and during infusion.

Extravasation management

• Extravasation can be prevented by stopping infusion immediately.
• Extravasated solution should be gently aspirated (do not flush the line).
• Start hyaluronidase Antidote; Remove needle/cannula
• Apply dry, warm compresses for 20 mins four times per day for up to two days.
• Elevate extremity (Perez Fidalgo 2012). Infuse the remaining vinblastine dose through a separate vein.

Hyaluronidase

• If the cannula has been in place, 1 to 6 mL Hyaluronidase (150 Units/mL) should then be administered. The usual dosage is 1 mL Hyaluronidase per 1 mL extravasated drug.
• Subcutaneous injections of 1 to 6mL (150 units/mL), should be done in a clockwise fashion, using 1mL for every 1mL extravasated drug.
• If the cannula has been removed, administer 5 separate 0.2mL injections subcutaneously into extravasation site (using a 25 gauge needle).

Intralesional (offer-label route).

• Vinblastine intralesional injections should be administered under local anesthesia.
• Vinblastine administration may require analgesics for up to two days.

Mechanism of action of Vinblastine:

• Vinblastine stops the cell in metaphase by disrupting formation of the mitotic spindle.
• It also inhibits the formation and formation of microtubules by binding to tubulin that is specific for the M or S phases.
• Vinblastine blocks glutamic acid utilization, which results in interference with protein synthesis and nucleic acid.

Metabolism:

• Occur in the liver (via CYP3A) to the active metabolite.

Half-life elimination:

• Terminal: 25 hours.

Excretion:

• Feces (10%);
• urine (14%)

International Brands of Vinblastine:

• Blastovin
• Blastovin PF
• Blestinib
• Cytoblastin
• Lemblastine
• Oncoblastin
• Oncostin
• Velbastine
• Velbe
• Vilban
• Vinatin
• Vinblastin
• Vinblastina
• Vinblastine Sulfate Injection
• Xintoprost

Vinblastine Brand Names in Pakistan: