Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

Abstract

BackgroundFew new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS).MethodsPatients receiving G 900 mg/m2 d 1, 8; D 75 mg/m2 d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate.ResultsFifty-one patients were included, with a median age of 17 years (8–71), 26 (51 %) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49 %) patients had metastases limited to lungs, 26 (51 %) multiple sites. Histology: 40 (78 %) osteosarcoma, 11 (22 %) HGS. Eight (16 %) patients achieved surgical complete response (sCR2) after GD.Four-month PFS rate was 46 %, and significantly better for patients with ECOG 0 (ECOG 0: 54 % vs ECOG 1: 43 % vs ECOG 2: 0 %; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75 % vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56 % vs HGS 18 %; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases.Forty-six cases had RECIST measurable disease: 6 (13 %) patients had a partial response (PR), 20 (43 %) had stable disease (SD) and 20 (43 %) had progressive disease (PD).The 1-year OS was 30 %: 67 % for PR, 54 % for SD and 20 % for PD (p = 0.005).ConclusionsGD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

Efficacy and safety of gemcitabine plus docetaxel in Japanese patients with unresectable or recurrent bone and soft tissue sarcoma: Results from a single-institutional analysis

“…For bone sarcoma, although the number of patients with response evaluable lesions was low in this study (n = 7), RR (14%) and DCR (86%) seemed comparable to those previously reported by other groups (RRs of 9–29% and DCRs of 41–57%) [21–24, 26]. Our results and the results reported by other groups, that is, that GD therapy seems to be more effective in bone sarcoma than in soft tissue sarcoma, suggest that GD therapy should be a preferred option, at least in some populations of patients with bone sarcoma.…”

Gemcitabine/nab‐paclitaxel for pediatric relapsed/refractory sarcomas

“…A direct comparison of toxicities of adults to children and adolescents is challenging, as most gemcitabine/nab‐paclitaxel clinical trials in adults have used different dosing schemas or included chemotherapy‐naïve patients. In one previous phase I/II trial which included pretreated patients, only patients ≥6 months from last therapy could enroll and only 23% of patients treated at the recommended phase 2 dose (RP2D) received prior chemotherapy . In regard to hematologic toxicity, which makes up the bulk of toxicity found in our patients, the RP2D cohort of this trial found Grade ≥3 neutropenia, anemia, and thrombocytopenia in 73%, 14%, and 28% of patients, respectively.…”

Advances in the management of osteosarcoma

“…How do we move forward? The optimal “conventional” chemotherapy regimen remains to be defined, and efforts to identify additional effective cytotoxic combinations, as exemplified by the demonstration of activity for the gemcitabine/docetaxel combination 73 , or to augment the usability of known effective agents by mitigating toxicities, exemplified by adding the cardioprotective agent dexrazoxane to increase doxorubicin exposure 74 , are ongoing. It would be very optimistic to expect anything but limited improvements from such approaches.…”