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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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High-Dose Chemotherapy for Multiply or Poor-Risk Relapsed Germ Cell Tumors.

Yago Nieto1, John F Ward2, Wayne Hofstetter3

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Sequential high-dose chemotherapy (HDC) with gemcitabine/docetaxel/melphalan/carboplatin (GemDMC) shows promising survival rates for relapsed germ-cell tumors (GCT). Bevacizumab did not improve outcomes in this study.

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Area of Science:

  • Oncology
  • Cancer Research
  • Pharmacology

Background:

  • Relapsed germ-cell tumors (GCT) have poor outcomes with standard treatments.
  • High-dose chemotherapy (HDC) with autologous stem-cell transplant offers a curative option for some GCT patients.
  • Novel therapeutic strategies are needed for multiply relapsed or refractory GCT.

Purpose of the Study:

  • To evaluate the efficacy of sequential gemcitabine/docetaxel/melphalan/carboplatin (GemDMC) with or without bevacizumab in patients with relapsed or refractory GCT.
  • To assess if bevacizumab, targeting GCT vascularity, synergizes with HDC.
  • To determine if this regimen can improve outcomes beyond expected rates.

Main Methods:

  • A trial involving sequential bevacizumab-GemDMC followed by bevacizumab-ifosfamide/carboplatin/etoposide (ICE) in three cohorts.
  • Eligibility criteria included second or later relapse or poor-risk first relapse.
  • Results were validated in an additional off-trial cohort.

Main Results:

  • 165 male patients with multiply relapsed/refractory GCT were treated.
  • Overall response rate was 84.5%, with 77% achieving complete or partial remission.
  • Five-year relapse-free survival (RFS) and overall survival (OS) rates were 57.1% and 58.3%, respectively.
  • No significant difference in outcomes was observed between patients who received bevacizumab and those who did not.

Conclusions:

  • Sequential GemDMC-(I)CE chemotherapy is effective in multiply poor-risk relapsed GCT, exceeding anticipated outcomes.
  • Bevacizumab did not demonstrate a significant benefit in improving RFS or OS in this patient population.
  • The established regimen provides a viable treatment option for patients with advanced GCT.