Combination of 5-Fluorouracil, Adriamycin, Ifosfamide and Cisplatin in Metastatic Adult Soft Tissue Sarcoma: Results of a Phase II Study

Abstract

Treatment results of advanced soft tissue sarcomas are still suboptimal. To evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5-fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study was initiated in patients with advanced soft tissue sarcomas of different histological subtypes. Fifty-six previously untreated patients with advanced soft tissue sarcomas of different histological subtypes (24 females, 31 males, median age 51.3 years, median Karnofsky performance status 80%) were included in this study. Treatment consisted of ADM 50 mg/m² i.v. on day 1, IFO 4,000 mg/m² i.v. on day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO administration, FU 500 mg/m² i.v. as 24-hour infusion on days 1 + 2, DDP 100 mg/m² i.v. on day 2. This regimen was repeated every 4 weeks for at least 2 cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56 patients. One toxic death due to severe neutropenia and fungal pneumonia occurred. Granulocyte colony-stimulating factor was administered in 8/35 neutropenic patients. Time to recovery was significantly reduced and no infectious complication was observed. WHO grade III/IV toxic diarrhea was observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with ondansetron alone. The overall response rate was 30.3%. The median duration of response (complete/partial response, CR/PR) was 18.1 months, the median progression-free interval was 4.5 months. The median survival time of all patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor-related pain was effectively reduced in 15/31 patients under treatment. FADIP produces comparable response rates to other standard treatment regimens in soft tissue sarcomas. Prolonged duration of response and median survival may be due to the use of continuous infusion of FU as a synergistic factor to alkylating agents. Granulocyte colony-stimulating factor is effective in reducing the otherwise observed high rate of WHO grade III/IV hematological toxicity with severe neutropenia.

Increase ofCandidacell virulence by anticancer drugs and irradiation

“…Iatrogenic fungal infection is a serious problem in immunosuppressive treatments. In patients who have undergone immunosuppressive chemotherapy for organ transplantation and chemoradiotherapy for malignant tumors, fungal pneumonia is sometimes a complication of therapy (13, 27, 42). However, the role of oral Candida cells in the systemic infection is unknown, although Candida cells living in the oropharynx appear to easily invade the bronchus and multiply in the lungs.…”

Increase ofCandidacell virulence by anticancer drugs and irradiation

“…Iatrogenic fungal infection is a serious problem in immunosuppressive treatments. In patients who have undergone immunosuppressive chemotherapy for organ transplantation and chemoradiotherapy for malignant tumors, fungal pneumonia is sometimes a complication of therapy (13, 27, 42). However, the role of oral Candida cells in the systemic infection is unknown, although Candida cells living in the oropharynx appear to easily invade the bronchus and multiply in the lungs.…”

Increase ofCandidacell virulence by anticancer drugs and irradiation

“…Iatrogenic fungal infection is a serious problem in immunosuppressive treatments. In patients who have undergone immunosuppressive chemotherapy for organ transplantation and chemoradiotherapy for malignant tumors, fungal pneumonia is sometimes a complication of therapy (13, 27, 42). However, the role of oral Candida cells in the systemic infection is unknown, although Candida cells living in the oropharynx appear to easily invade the bronchus and multiply in the lungs.…”

Increase ofCandidacell virulence by anticancer drugs and irradiation

“…Iatrogenic fungal infection is a serious problem in immunosuppressive treatments. In patients who have undergone immunosuppressive chemotherapy for organ transplantation and chemoradiotherapy for malignant tumors, fungal pneumonia is sometimes a complication of therapy (13, 27, 42). However, the role of oral Candida cells in the systemic infection is unknown, although Candida cells living in the oropharynx appear to easily invade the bronchus and multiply in the lungs.…”