[Current state of neoadjuvant therapy of soft tissue sarcoma]. / Aktueller Stand der neoadjuvanten Therapie bei Weichteilsarkomen.

The treatment of soft tissue sarcoma is clinically challenging. Referral to an experienced center with an interdisciplinary team is strongly recommended. Neoadjuvant therapy, including irradiation and chemotherapy, has been applied to improve local control rates, eradicate micrometastases and assess chemosensitivity. However, the role of neoadjuvant therapy remains controversial, especially for systemic therapy, as the only available randomized trial failed to prove a benefit for survival. Nevertheless, on the basis of the current body of literature, neoadjuvant therapy can be considered on an individual basis for patients with high-risk tumors. Whenever possible, patients should be included in a clinical trial.

Changes induced by surgical and clinical factors in the pharmacology of intraperitoneal mitomycin C in 145 patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated. MATERIALS AND METHODS: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined. RESULTS: The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space (p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced (p = 0.0001) drug concentrations in the plasma. CONCLUSIONS: Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics.

Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral high-risk soft tissue sarcomas.

PURPOSE: To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS). PATIENTS AND METHODS: From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation. RESULTS: Objective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T(min)) and time-averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) of all measured tumor sites differed significantly between responders and nonresponders (T(min), 39.3 degrees C v 38.0 degrees C; P =.002; T(50), 40.9 degrees C v 40.3 degrees C; P =.038; T(90), 40.1 degrees C v 39.3 degrees C; P =.017). At 5-year follow-up, probability of LFFS (59% v 0%; P <.001) and OS (60% v 10%; P <.001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy. CONCLUSION: Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.

Ukrain treatment of a patient with retroperitoneal synovial sarcoma. Case report.

A 23-year-old woman, diagnosed with a synovial sarcoma of the peritoneum, underwent an operation for tumor extraction. In the postoperative period, Ukrain was injected i.v. at a dose of 10 mg on alternate days, for a total of 10 injections. After a 2-month break, this schedule was repeated. Ukrain treatment was well tolerated by the patient and there were no complications in the postoperative period. The following changes in immunohematological parameters were observed: increased total leucocytes, T lymphocytes and T helpers. Nearly 4 years after Ukrain therapy, the patient is in complete remission.

Retroperitoneal soft tissue sarcoma: effect of hyperthermic total abdominal perfusion.

AIMS AND BACKGROUND: Soft tissue sarcomas (STS) of the retroperitoneum are rare tumors. Surgery remains the principal modality of therapy in the management of primary and recurrent retroperitoneal STS. However, little is known about the effect of regional chemotherapy using hyperthermic total abdominal perfusion (HTAP). We analyzed independent prognostic variables in 33 patients with STS in the retroperitoneum admitted from November 1990 through December 1996. METHODS AND STUDY DESIGN: Data regarding patients' age, gender, tumor size, histological tumor type, tumor location, type of operation (primary or secondary surgery), extent of surgical management (marginal or extended), use of HTAP, tumor grade, and tumor stage according to the TNM classification were examined by univariate and multivariate analyses. RESULTS: All 33 patients underwent complete resections (marginal or extended). Eleven of them received locoregional chemotherapy by HTAP. The overall cumulative 5-year survival rates in patients with stage IIA and advanced disease were 82% and 22%, respectively (log-rank test, P<0.01). Using Cox's proportional hazard model, tumor stage, use of HTAP and type of operation were found to have significant influence on overall survival (P<0.05). CONCLUSIONS: Our results showed that complete resection along with HTAP chemotherapy may improve survival in patients with retroperitoneal STS. These phase II data could be used to support the initiation of a phase III trial to test HTAP in patients submitted to complete resection of retroperitoneal STS.

[Clinical reevaluation of continuous intravenous infusion of 5-fluorouracil--plasma concentrations and clinical dose by continuous intravenous and 60-min infusions].

Daily and intermittent continuous intravenous infusions [by gravity drip, (IVG) or infusion pump, (IVP)] and intermittent short-time intravenous drip infusion of 5-FU were carried out on advanced cancer patients. The MTD and dose-limiting toxicity were investigated in relation to the plasma concentrations of 5-FU determined by HPLC. Responses in eleven patients receiving IVG administration daily at 8-21 mg/kg/day were NC, but those given 5-FU alone showed no adverse reactions. Plasma concentrations were too low to be determined. In 9 patients receiving IVG or IVP administration weekly at 60 mg/kg for 24 hr, 1 of the 5 evaluable patients showed reduced hepatic metastatic lesions. One of 4 patients receiving IVP administration weekly at 120 mg/kg for 48 hr showed a disappearance of metastatic lesions in the skeletal muscle, but bone marrow suppression was observed as dose-limiting toxicity. Pharmacokinetics were more stable in IVP than in IVG with less individual difference in the plasma concentrations. Among the outpatients receiving short-time iv, IVG administration once or twice a week, 2 patients given weekly administrations at 20 mg/kg for 60 min showed slight adverse reactions. In 6 patients given high-dose administrations, bone marrow suppression was observed. When pharmacokinetics in the patients given 5-FU for 60 min were compared between the IVG and IVP groups, there were individual differences in plasma concentrations, but the differences were not significant. It was concluded from above results that the following practical dose schedules would be recommendable: 60 mg/kg for 24hr/week by IVP for inpatients and 20 mg/kg for 60 min/week by IVG for outpatients.

Chemotherapy of refractory germ cell cancer with Etoposide.

Eighteen patients with advanced germ-cell cancer (12 primary gonadal, six extragonadal) that was refractory to vinblastine (V), cisplatin (P), and bleomycin (B) were treated with Etoposide (VP-16-213) and cisplatin +/- bleomycin sulfate +/- doxorubicin hydrochloride. All patients experienced nausea, vomiting, alopecia, and myelosuppression. There were no treatment-related deaths. Five (42%) of 12 patients with primary gonadal germ-cell cancer achieved a complete remission and are presently alive with no evidence of disease. None of the six patients with extragonadal germ-cell cancer achieved a complete response. Thirteen patients died 6.2 months (median) after starting Etoposide treatment. Etoposide-containing chemotherapy is useful in patients with primary gonadal germ-cell cancer. Alternative therapies are needed for patients with extragonadal germ cell cancer.