Combination Irinotecan & Vincristine Active Against Metastatic Rhabdomyosarcoma.

Combination of Irinotecan and Vincristine Active Against Metastatic Rhabdomyosarcoma

According to the results of a study published in the Journal of Clinical Oncology, treatment with the chemotherapy drugs irinotecan and vincristine reduced or eliminated detectable cancer in roughly 70 percent of children with metastatic rhabdomyosarcoma.

Rhabdomyosarcoma is a soft-tissue cancer that arises from skeletal muscle. It is the most common soft-tissue sarcoma among children. The extent of spread of the cancer from its site of origin helps guide treatment decisions for patients with this disease; therefore, accurately determining the extent or presence of cancer spread is important in order to give patients optimal treatment choices.

Because cure rates for children with high-risk metastatic rhabdomyosarcoma remain suboptimal, researchers continue to evaluate alternative treatment regimens. To explore the response of metastatic rhabdomyosarcoma to treatment with the chemotherapy drugs irinotecan and vincristine, researchers conducted two clinical trials among patients under the age of 21 years with newly diagnosed metastatic rhabdomyosarcoma or undifferentiated sarcoma.

In the first trial, patients were initially treated with irinotecan alone. Patients who experienced a partial or complete disappearance of cancer after two cycles of irinotecan then received additional treatment with irinotecan and vincristine alternating with the commonly used VAC chemotherapy regimen (vincristine, dactinomycin, and cyclophosphamide). Patients who did not respond to treatment with irinotecan received additional treatment with VAC alone.

The second trial had a similar design, but evaluated the combination of irinotecan and vincristine, rather than irinotecan alone. Patients who responded to irinotecan and vincristine received additional treatment with these two drugs alternating with VAC. Patients who did not respond to irinotecan and vincristine received additional treatment with VAC alone.

  • The first trial was closed early due to a high rate of progressive disease (32%) among children who were initially treated with irinotecan alone. The researchers note, “The unexpectedly high rate of progression seen with irinotecan alone precludes us from recommending the use of this single agent for the treatment of rhabdomyosarcoma.”
  • In the second trial, which evaluated initial treatment with the combination of irinotecan and vincristine, 70% of children experienced a partial or complete disappearance of detectable cancer, and only 8% experienced progressive disease.
  • In spite of the promising response rate, survival among children initially treated with irinotecan and vincristine was similar to that among children treated with VAC alone.
  • Gastrointestinal problems (abdominal pain, diarrhea, and dehydration) were the most common side effects among children treated with irinotecan and vincristine.

The researchers conclude that the combination of irinotecan and vincristine is highly active against metastatic rhabdomyosarcoma, and that this combination warrants further testing in intermediate-risk patients with rhabdomyosarcoma. The researchers note that the combination of irinotecan and vincristine has a different mechanism of action than the VAC chemotherapy regimen and produces different side effects.

Reference: Pappo AS, Lyden E, Breitfeld P et al. Two consecutive Phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the children’s oncology group. Journal of Clinical Oncology. 2007;25:362-369.

Related News:Molecular Markers Detect Cancer Spread in Rhabdomyosarcoma (3/31/2006)

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