High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors

Area of Science:

• Oncology
• Hematology
• Cancer Research

Background:

• Refractory metastatic solid tumors present a significant clinical challenge.
• Limited effective treatment options exist for patients with advanced-stage cancers.
• High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) is a potential strategy for aggressive malignancies.

Purpose of the Study:

• To evaluate the safety and efficacy of escalating doses of cyclophosphamide (Cy) and carmustine (BCNU) followed by ABMT.
• To determine the maximum tolerated dose (MTD) of the Cy + BCNU regimen.
• To assess treatment response rates, duration, and toxicity in patients with refractory metastatic solid tumors.

Main Methods:

• Twenty-six adult patients with refractory metastatic solid tumors received high-dose Cy + BCNU on escalating dose schedules.
• Autologous bone marrow transplantation (ABMT) was performed following chemotherapy.
• Toxicity, dose-limiting toxicities, and MTD were recorded.
• Response was evaluated by at least a 50% reduction in measurable tumor.
• Hematologic recovery (WBC and platelet counts) was monitored post-ABMT.

Main Results:

• The maximum tolerated dose was determined to be Cy 160 mg/kg and BCNU 900 mg/m2.
• Severe, dose-related toxicity was observed.
• Median WBC recovery was 13 days, and platelet recovery was 22 days post-ABMT.
• Eighty percent (16/20) of evaluable patients responded, with three achieving complete remission (CR).
• Response rates varied by tumor type: breast carcinoma (8/9), melanoma (2/5), sarcoma (2/2), and colon carcinoma (4/4).

Conclusions:

• High-dose cyclophosphamide and carmustine with ABMT can induce responses in refractory metastatic solid tumors.
• Toxicity is significant and dose-dependent.
• Short response durations and early relapses highlight the need for earlier intervention.
• Applying this intensive therapy earlier in the disease course may improve overall survival outcomes.