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Cancer treatment

Nonreplicating Adenoviral Vector Combines With Chemotherapy for Primary Breast Cancer Shows Promising Results

Strategic Insights

— 2 min read

A recent study has reported on the use of a nonreplicating adenoviral vector (Ad5) that contains the wild-type p53 transgene combined with chemotherapy as a novel gene-therapy approach for primary breast cancer. The study, led by M. Cristo-Fanilli and colleagues at the University of Texas, involved 13 patients with locally advanced breast cancer who received 6 cycles of primary systemic therapy consisting of intratumoral injections of Ad5CMV-p53, docetaxel, and doxorubicin, followed by surgery. The results showed that all 12 evaluable patients achieved an objective clinical response, and the surgical specimens revealed scattered tumor cells with extensive tumor-infiltrate leukocytes. The study was terminated early due to lack of pathologic complete response, but the researchers concluded that Ad5CMV-p53 combined with PST is safe, active, and associated with local immunomodulatory effects.

Key Takeaways:

  • The study used a nonreplicating adenoviral vector (Ad5) that contains the wild-type p53 transgene combined with chemotherapy as a novel gene-therapy approach for primary breast cancer.
  • The study involved 13 patients with locally advanced breast cancer who received 6 cycles of primary systemic therapy consisting of intratumoral injections of Ad5CMV-p53, docetaxel, and doxorubicin, followed by surgery.
  • All 12 evaluable patients achieved an objective clinical response, and the surgical specimens revealed scattered tumor cells with extensive tumor-infiltrate leukocytes.
  • The median age of the patients was 56 years (range, 39-71 years), and the median tumor size was 8 cm (range, 5-11 cm).
  • Eight patients (73%) had a p53 mutation, while the remaining 5 patients (46%) had normal p53 status.
  • Serial biopsies showed an increase in p53 messenger RNA (mRNA) and p21(WAF1/Cip1) mRNA.
  • The study was terminated early due to lack of pathologic complete response, but the researchers concluded that Ad5CMV-p53 combined with PST is safe, active, and associated with local immunomodulatory effects.
  • The promising clinical activity of this combination deserves further investigation in randomized studies.

Statistics:

  • 13 patients were involved in the study.
  • 12 evaluable patients achieved an objective clinical response.
  • The median age of the patients was 56 years (range, 39-71 years).
  • The median tumor size was 8 cm (range, 5-11 cm).
  • 8 patients (73%) had a p53 mutation.
  • Serial biopsies showed an increase in p53 messenger RNA (mRNA) and p21(WAF1/Cip1) mRNA.
  • 4 patients (30%) developed systemic recurrence, and 2 patients died at a median follow-up of 37 months (range, 30-41 months).
  • The estimate breast cancer-specific survival rate at 3 years was 84% (95% confidence interval, 65.7-100%).

Sources:

  • Cristofanilli, M., et al. "Safety, efficacy, and biologic activity of a novel gene-therapy approach combining a nonreplicating adenoviral vector that contains the wild-type p53 transgene with chemotherapy in patients with primary breast cancer: a phase I trial." Cancer 107.5 (2006): 935-944.

(Note: exact citation as provided in the original text)

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