Chemotherapy

Adjuvant Chemotherapy in Sarcoma

Soft tissue sarcomas (STS) are relatively rare tumours. Studies of adjuvant chemotherapy in patients with STS are few. Moreover, randomised studies of adequate size of patient population required to detect or exclude a significant benefit are even fewer and conflicting. The reasons for misleading results encounter small numbers of patients, neoadjuvant treatment, low dose intensity in several studies, and inclusion of low grade STS among the treated population of high grade sarcoma patients [1].

The old combination of cyclophosphamide, vincristine, adriamycin and dacarbazine (CYVADIC) used as an adjuvant treatment in soft tissue sarcoma failed to improve the patients survival [2]. CYVADIC was given to 145 patients following complete surgical resection with or without radiation therapy, while 172 other patients remained on follow-up. For a median follow-up of 80 months, The relapse-free survival was better for the CYVADIC arm (p=0.007), and resulted rather from reduced local recurrence rate (17% in CYVADIC Vs. 31% in control arm; p=0.004) than from metastatic spread, which was similar in both arms. It was concluded that adjuvant CYVADIC could not be recommended outside a clinical trial [2].

The introduction of ifosfamide into the anti-sarcoma drug arsenal gives a
strong rationale for continued investigation of preoperative and or adjuvant chemotherapy. Adriamycin plus Ifosfamide with granulocyte-colony-stimulating factor (G-CSF) support are being studied in STS patients at high risk for local or systemic relapse. Long term follow-up results using ifosfamide-based adjuvant combination chemotherapy are still lacking.

The lack of clear benefit in the reported trials is related to their design and methodology. To overcome the problem of small sample size in many of the randomised trials, a meta-analysis using individual patient data is being conducted by the Medical Research Council. Preliminary results of the meta-analysis have been reported in Paris last year [3]. According to the meta-analysis, the 5-year data with 95% confidence interval values, for the group getting chemotherapy, are improved local control in 5% (1-10%; p=0.02), reduced risk of metastases in 9% (5-13%; p=0.003) and improved 5-year survival in 4% (-1 to 9%; p=0.09). The advantages for chemotherapy in preventing local recurrence and metastases are most reliable in patients with extremity lesions and in patients with liposarcomas, MFH and synovial sarcoma. The survival advantage remains, however, modest and statistically insignificant.

In conclusion, systemic adjuvant chemotherapy for adult patients with high grade soft tissue sarcoma remains controversial and investigational. The existing literature on STS can neither recommend nor disapprove the case of adjuvant chemotherapy.
Decision making becomes difficult when there are no clear guidelines, especially when literature data should be discussed with the patient.