Impact of neoadjuvant chemotherapy on postoperative morbidity in soft tissue sarcomas.

PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309 patients who presented to The University of Texas M.D. Anderson Cancer Center for definitive surgical management of primary soft tissue sarcomas were retrospectively reviewed. One hundred five patients who received NeoCT were compared with 204 patients who had surgery first (Surg). Patients had extremity sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors (median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were younger (median age 47 v 55 years). The incidence of surgical complications was not different for NeoCT patients than for Surg patients, both in those with extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral sarcomas (29% v 34%). The most common complications were wound infections and other wound complications. Preoperative radiation therapy, autologous flap coverage, and extremity tumors were associated with increased wound complications. No significant differences in length of hospital stay, rate of readmission, or rate of reoperation for complications were found between the NeoCT and Surg groups. One of the three postoperative deaths in our series occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was no evidence that NeoCT increased postoperative morbidity in patients with soft tissue sarcomas. Prospective, randomized studies are needed to confirm these results.

Phase II study of CI-980 (NSC 635370) in patients with previously treated advanced soft-tissue sarcomas.

Doxorubicin and ifosfamide are the two most active agents in the treatment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore, important to identify newer drugs with activity against this disease. CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin and blocks cell cycle progression in mitosis. Given its broad spectrum activity against several solid tumor models in vivo, we decided to perform a phase 2 study of this drug in previously treated soft-tissue sarcomas. A total of 18 eligible and evaluable patients were entered in the first stage of the trial. The median age was 53 yrs (range, 17-72). No objective responses have been noted. Six patients had stable disease after a median of 3.5 cycles of chemotherapy while 12 others had progressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m2/d x 3). The median AGC nadir was 1.2/microl(0.1 -4.7) on day 10 and the median platelet nadir was 150,000/microl (31,000-338,000). Twenty cycles were complicated with grade 3-4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade 1 thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one cycle. In conclusion, CI-980 was well tolerated at this dose and schedule but inactive in soft-tissue sarcomas.

Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer.

BACKGROUND: Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. OBJECTIVE: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. DESIGN: Phase I and II clinical cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. PATIENTS: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. INTERVENTION: A single intravenous dose of thrombopoietin (0.3 to 2.4 micrograms/kg of body weight) 3 weeks before chemotherapy. MEASUREMENTS: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. RESULTS: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. CONCLUSIONS: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.