page_title: VAMP regimen
section_title: History
hierarchical_section_title: VAMP regimen / History
context_page_description: VAMP regimen or VAMP chemotherapy is a four-drug combination chemotherapy regimen, used today in the treatment of Hodgkin lymphoma. It was one of the earliest combination chemotherapy regimens, originally developed as a treatment for childhood leukemia by a group of researchers at the National Cancer Institute led by Emil Frei and Emil Freireich. The first clinical trial of VAMP began in 1961. Because it was the first time that four chemotherapeutic agents were used at once, the trial was highly controversial at its time. Although new combination chemotherapy regimens have replaced the use of VAMP in the treatment of childhood leukemia, VAMP is considered an important precursor to modern treatments, confirming the effectiveness of combination chemotherapy and leading to the use of combination chemotherapy regimens to treat other types of cancer.
  The VAMP regimen developed by Freireich and Frei was a combination of vincristine, amethopterin, mercaptopurine, and prednisone. Now, other combinations and doses that are referred to as VAMP, including C-VAMP and a VAMP regimen that replaces the mercaptopurine of the original combination with doxorubicin.
context_section_description: By 1960, several chemotherapeutic agents had emerged, among these nitrogen mustards, antifolates, and purine analogs, each with their own individual history and development. Furthermore, the work of Howard Skipper, who argued that every remaining cancer cell in the body must be eradicated in order to ensure the survival of the patient, shifted clinical practice towards more aggressive chemotherapy regimens. Importantly, Skipper also established that the use of multiple chemotherapy drugs at once provided synergistic benefits over single agents. However, the idea of combination chemotherapy was initially met with resistance by researchers concerned about the toxicity of multiple harmful drugs being used simultaneously.
  VAMP emerged amid a period of cautious and methodical testing of various combinations of chemotherapeutic agents. Due to the immense possibilities of combinations and the potential dangers of these aggressive regimens, this trial process was slow and, in the view of some, inefficient.
  Emil Frei and Emil Friereich, researchers at the National Cancer Institute (NCI), took bold and decisive action, proposing a regimen of four chemotherapeutic agents, more drugs than had ever been previously attempted. The aggressiveness and potential lethal toxicity of this proposal was alarming to many fellow members of the NCI, who felt that Frei and Freireich were making a dangerous break with the systematic trial processes that characterized the leukemia group of the NCI. However, Frei and Freireich felt that the current pace of the NCI was too slow to make progress.
  Initially, the leukemia group rejected the VAMP proposal, denying funding until many of their current trials had been completed. However, an arrangement was reached that involved the VAMP trial being run separately from the rest of the leukemia group at the NCI. The trial began in 1961 on children with leukemia.
  In the initial weeks, the children were pushed to the brink of death by VAMP's four chemotherapy agents, each cytotoxic on its own. After a few weeks, however, the children's marrow healed, remissions came, and leukemia was undetectable in many of the patients. These remissions astounded Frei and Freirdrich's peers, and gained supporters even from those who formerly resisted the trial. The remission rate ultimately increased to 60%, and around half of those remissions lasted for several years.
  
  However, the remissions were not permanent for most. Because none of the components of VAMP could cross the blood–brain barrier, there was nothing stopping the leukemia from reemerging in the nervous system and invading the brain. These relapses proved deadly for all but a few.
caption: Molecular structure of Vincristine
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