Concomitant chemo-radiotherapy in the treatment of locally advanced and/or metastatic soft tissue sarcomas: experience of the National Cancer Institute of Genoa.
Previous in vitro and in vivo studies showed a synergistic effect of concomitant doxorubicin and radiotherapy in a variety of solid tumors. From 1988 to 2000, we have investigated in a pilot study and then in a phase II study the efficacy of a concomitant doxorubicin radiotherapy treatment in patients with advanced and/or metastatic soft tissue sarcomas (STS). We enrolled and treated a group of 115 patients with advanced STS, with metastases (61%), frequently pretreated (59%), predominantly G2/G3 (84%). Doxorubicin was administered by continuous infusion at a dose of 12 mg/m(2)/day over 5 consecutive days concomitantly with radiotherapy; treatment was given on ambulatory basis at 2-week intervals with support of granulocytes colony stimulating factors (GCSF). In the whole group of 115 patients a clinical objective response (ORs) rate of 67% was obtained, with 11% complete and 56% partial responses. No patient progressed while on therapy, except one who progressed in non-irradiated metastatic tumor. Treatment (median 3 cycles) was well tolerated with no WHO grade 3 toxicity (apart from alopecia) and no acute or chronic cardiotoxicity. Thirty-nine responder patients underwent surgery (24 primary tumors, 10 relapses, 5 relapses plus isolated lung metastases). The median survival time(s) was 29 months in the whole series and over 50 months in responder patients. A multivariate analysis showed a positive association between survival and sex (HR=1.8; CI 95%, 1.0-3.4), performance status (HR=2.1; CI 95%, 1.1-4.0), ORs (HR=7.9; CI 95%, 3.5-18.1) and surgery (HR=8.8; CI 95%, 2.1-35.9). Low toxicity, high OR rate and positive survival time trend make the concomitant chemo-radiotherapy an efficacious approach for advanced STS.
Toma
Salvatore
S
Department of Oncology, Biology and Genetics, University of Genoa, National Institute for Cancer Research, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. toma@cba.unige.it
Canavese
Giuseppe
G
Grimaldi
Andrea
A
Ravera
Giambattista
G
Ugolini
Donatella
D
Percivale
Pierluigi
P
Badellino
Fausto
F
D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome
D004317:Doxorubicin