Adriamycin and Cis-Platinum as First-Line Treatment in Unresectable Locally Advanced or Metastatic Adult Soft-Tissue Sarcomas

Abstract

Standard chemotherapy in advanced adult soft-tissue sarcomas (STS) has not yet been established. We evaluated the efficacy and toxicity of the combination of adriamycin (ADR) and cis-platinum (CDDP) as first-line treatment in nonoperable locally advanced or metastatic adult STS. Thirty patients were treated with CDDP 100 mg/m2 on day 1 and ADR 75 mg/m2 equally divided on days 1 to 3, every 3 weeks for 6 cycles. Patients were evaluated for response, toxicity, and survival, while resectability of residual disease was also assessed after the third cycle and the end of chemotherapy. No complete response was observed. Five patients (16.7%, 95% CI: 2.5%-31%) achieved partial response, 16 patients (53.3%, 95% CI: 34%-72%) had stable disease and 9 patients (30%, 95% CI: 13%-47%) had progressive disease. The overall median survival was 11.5 months (range, 4-96 months), and the median time to disease progression was 6 months (range, 0-96 months). Furthermore, two patients with PR and six patients with stable disease underwent further surgery followed by radiotherapy in four of them. At present, 5 patients remain free of relapse for 96, 90, 72, 60, and 48 months, respectively. Treatment-related toxicity was acceptable, with moderate myelosuppression and alopecia as the main adverse events. The ADR/CDDP regimen was well tolerated, but it did not achieve a high response rate. However, patients with resectable disease after chemotherapy achieved long-term survival. Further studies are needed to evaluate the role of combined-modality treatments in the management of patients with advanced STS.

MCM4 Is a Novel Biomarker Associated With Genomic Instability, BRCAness Phenotype, and Therapeutic Potentials in Soft-Tissue Sarcoma

“…Besides, targeting the HR and non-homologous end-joining (NHEJ) mechanism of cancer cell might further enhance such therapeutic sensitivity of the cancer cells with high levels of CNVs (Gregg et al, 1993;Zhang et al, 2014). However, previous clinical trials of PARPi and DNA-damaging agents mostly failed to confirm such vulnerability in unselected sarcoma population (Kalofonos et al, 2004;Choy et al, 2014). Interestingly, our study demonstrated that genomic instability and BRCAness phenotype could vary tremendously, both inter-and intrain STS subtypes, which were correlative with tumoral MCM4 expression.…”

Phase I trial of gemcitabine, doxorubicin and cisplatin (GAP) in patients with advanced solid tumors

“…G and A were used in combination in a phase I/II trial on transitional cell carcinomas of the urothelial tract that demonstrated a good toxicity profile and promising activity. A and P have been combined in the treatment of endometrial carcinoma and sarcoma [4,5]. A phase II study of the same combination in 18 patients with renal cell carcinoma reported two complete responses (CRs) and five PRs with no grade 4 toxicities [2].…”

A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS)

“…4 A variety of combination regimens has been studied in phase II and III trials and most of them have included adriamycin. [5][6][7][8] Most of these studies have suggested that combination chemotherapy may result in higher response rates than single-agent doxorubicin. Epirubicin, which is an analogue of doxorubicin with less cardiotoxicity but equal efficacy, 9 has been used as single agent and in combination regimens for the treatment of STS.…”