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Oral Etopodise (VP-16) For Brain Tumors

By Kerryn Brookes

Last Updated: 7/10/99

  • CHEMOTHERAPEUTIC DRUG NAME: VP-16 / ETOPOSIDE
  • DOSAGE: ORAL:
    • Pediatric Patients: 30 - 60mg per day    28 day cycle/ 21 on, 7 off
    • Adult Patients: 50 - 100mg per day     28 day cycle/ 21 on, 7 off
  • LENGTH OF ADMINISTRATION: 12 - 24 months or until PD
  • MECHANISM OF ACTION: Topoisomerase II inhibitor
  • COMMON SIDE EFFECTS: Partial alopecia, Nausea, Vomiting, Diarrhoea, Weight loss, Neutropenia, Thrombocytopenia
  • RARE SIDE EFFECTS: Chills, fever, tachycardia, bronchospasm, peripheral neuropathy, CNS toxicity, liver toxicity, renal toxicity, aftertaste, rash, pruritus, pigmentation, constipation, dysphagia, transient cortical blindness, radiation recall dermatitis, myocardial infarction, cardiotoxicity, teratogenicity
  • LONG-TERM SIDE EFFECTS: Acute Myelogenous leukemia

REVIEW BY A PARENT OF A PEDIATRIC PATIENT:

Oral VP-16 is one of the mildest chemotherapeutics available at this time. The side effects are minimal and it provides the patient with a high quality of life. Nausea can be easily combated with oral Zofran or Kytril. Hair loss is minimal and as the course progresses hair may regrow while still on treatment. Most of the side effects appear to be transient rather than on-going and do not cause the patient too much discomfort. Although neutropenia occurs quite often it is tolerable and isolation from the community is not required. The results in my child have been excellent and although this drug is not curative it certainly would be first choice for quality of life.

FROM A MEDICAL VIEW POINT:

Etoposide is a topoisomerase II inhibitor which has been used for over 20 years in the treatment of a variety of malignancies. However, a low-dose oral approach is relatively new and further investigation is still being pursued. Studies published thus far have shown oral etoposide to be well tolerated with modest toxicity[1]. Oral VP-16 appears to be active and effective in management of malignant gliomas[2] and has been demonstrated to be effective in the treatment of SCLC, malignant lymphoma and ovarian cancer[4].

In the preliminary results of a phase II trial into VP-16 for malignant gliomas 32 patients with grade 3 or 4 gliomas were evaluated with 6 patients obtaining CR and 11 patients obtaining PR, providing an objective response rate of 50.4% All patients receive concurrent radiotherapy[2].

In a study of recurrent brain-stem gliomas 12 patients ranging in age from 1 to 49 years were treated with 50mg/m2/day for 21 consecutive days followed by a 14 day break. All patients had pathologic diagnosis of a grade 3 or 4 glioma and had had prior radiotherapy, with 5 patients having had prior treatment with nitrosoureas. There was a 50% response with 1 CR, 3 PR and 2 SD with a median response time of 8 months and a response duration of 4-20 months. 10 of the 12 patients have since died from progressive disease[1].

A study of oral VP-16 in 7 patients with medulloblastoma, aged 4 to 16 years resulted in 6 patients with PR after at least 2 courses and the remaining patient having SD. At the conclusion of the study all patients had had between 2 and 8 courses and 4 patients were continuing to respond. 2 patients had progressive disease.[3]

Another study of 14 children ranging in age from 4 to 18, with recurrent supratentorial gliomas was conducted. All patients had either a grade 3 or 4 glioma and had had prior radiotherapy and nitrosoureas. Cycles were 21 days on 14 days off. Response rate was 50% with 3 patients having PR and 4 patients having SD.

8 children suffered partial alopecia, 6 diarrhea, weight loss - 4, anemia - 4, neutropenia - 4 and 4 patients required red blood cells while 3 required platelets. [5]

CONCLUSION: Oral etoposide has been used as a single agent in the treatments reviewed above, however it has also been used in combination with other agents with some degree of success. The oral approach has proven to be effective in producing a response from various malignancies and the overall response rate in brain neoplasms would appear to be somewhere in the region of 50%. It has also proven to be mild with the majority of patients not suffering any significant toxicities other than neutropenia. Etoposide is schedule dependent therefore creating different responses in patients who have received intravenous etoposide versus oral etoposide.

References:


[1]. M.Chamberlain: Recurrent brainstem gliomas treated with oral VP-16. J.Neuro-Oncology 15:133-139,1993

[2]. P.Beauchesne, C.Soler, F.Dubois, J.Brunon: Preliminary results of a phase II trial using etoposide as a first line therapy for malignant gliomas. Abstract of the Annuals meetings of the American Society of Clinical Oncologists (1998)

[3] D.Ashley, L.Meier, T.Kerby, F.Zlduondo, H.Friedman, A.Gajjar, L.Kun, P.Duffner, S.Smith, D.Longee: Response of recurrent medulloblastoma to low-dose oral etoposide. J.Clin.Oncol,Vol 14, No 6(June), 1996:pp 1922-1927

[4] X.Zhang, H.Zhu, J.Xu: Clinical trial of oral etoposide in the treatment of malignancies. Chung Hua Chung Liu Tsa Chih 1995 nov 17:6 454-7.

[5] M.Chamberlain: Recurrent supratentorial gliomas in children. Long-term salvage therapy with oral etoposide. Arch Neurol 1997, May, 54:5 554-8




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