Chemotherapy For Soft Tissue Sarcomas Research Articles

High-dose chemotherapy in soft tissue sarcoma?

High-dose chemotherapy in soft tissue sarcoma?

505 - Neoadjuvant long-term continuous intra-arterial chemotherapy of soft tissue sarcomas

505 - Neoadjuvant long-term continuous intra-arterial chemotherapy of soft tissue sarcomas

Primary resection of soft-tissue sarcomas: yes and no.

The primary tumour site is the most common origin in relapses of soft-tissue sarcomas (75%). Therefore, prevention of a relapse depends mainly on local tumour control in the primary therapeutic regimen. There are three modalities of treating children with sarcomas: surgical removal, radiation therapy and systemic chemotherapy. The aim is to reach a complete removal of the primary tumour and to preserve all vital and functionally useful structures. Under this aspect we evaluated the results of 22 patients, treated for soft-tissue sarcoma at the University Children's Hospital, Zurich, between 1989 and 1995. The age of the patients ranged between 3 and 16 years. The tumours of 11 patients were primarily resected, but in 9 patients the removal was incomplete (7 microscopically, Z macroscopically). Only 2 patients had a complete primary removal of their tumours, both being paratesticular sarcomas. In 11 patients an incisional biopsy was performed. Two of these patients had stage IV initially. Two tumours were removed completely in a second operation. Six patients did not need any further resections because of a very good response to chemotherapy. In 1 patient with unresectable tumour it was possible to remove the tumour almost completely after primary chemotherapy. Our experience with primary chemotherapy in soft tissue sarcomas showed the following advantages: 1. The low morbidity after biopsy allows a rapid beginning of the treatment. 2. In case of a very good response to chemotherapy it is possible to avoid a second operation. 3. The information of a poor response to chemotherapy makes the decision for an extensive surgery easier. 4. The possibility of a delayed, but complete removal of a primarily unresectable tumour will be more likely after chemotherapy. 5. Only a small group of tumours should be considered for removal during a primary surgical procedure.

Adjuvant chemotherapy of soft tissue sarcomas.

Soft tissue sarcomas tend to metastasize early and hematogenously. Therefore, and despite increasing possibilities of achieving optimal local control by surgery with or without radiotherapy, more than half of patients will die from metastases [1–4], Clearly, only the elimination of hematogenously borne micrometastases will make a major impact on the survival of these patients. As a result, interest in the use of chemotherapy as an adjunct to local treatment (adjuvant chemotherapy), has developed even though the response rates achieved with single-agent or combination chemotherapy for advanced or metastatic soft tissue sarcomas have been modest.

Chemotherapy for soft tissue sarcomas. Indications and advances.

(1997). Chemotherapy for soft tissue sarcomas. Acta Orthopaedica Scandinavica: Vol. 68, The Scandinavian—Australian Symposium on the Management of Bone and Soft Tissue Sarcomas, pp. 133-138.

A Phase I/II Study of a 72‐h Continuous Infusion of Etoposide in Advanced Soft Tissue Sarcoma

Purpose. The study was performed to assess the antitumour activity and toxicity of a 72-h continuous infusion of single-agent etoposide as second-line treatment for patients with locally advanced or metastatic soft tissue sarcoma (STS), following reports of substantial activity using this schedule of etoposide administration as first-line treatment in combination with ifosfamide. Patients/method. This was an open phase I/II trial performed at a single institution in patients with metastatic or locally advanced STS who had failed first-line treatment with doxorubicin + ifosfamide combination chemotherapy or, less commonly, single-agent treatment with doxorubicin or ifosfamide. Etoposide was given as a continuous intravenous infusion over 72 h. The starting dose level was 200 mg m-2 day-1 × 3 escalating in 10% steps in cohorts of three patients until dose-limiting toxicity was encountered. Results. Seventeen patients were treated, median age 47 years (range 26–71 years). No responses were seen in 16 assessable patients despite etoposide levels in the cotoxic range. The steady-state plasma concentration exceeded 8 μg ml−1 in all patients and in patients treated at ≥ 600 mg m −2 the mean steady-state level was 14.4 μg ml −1. The median event-free survival was 6 weeks (95% confidence interval (CI) 3.31–8.69) and the overall survival 16 weeks (95% CI 9.28–22.72). The maximum tolerated dose in this pretreated patient group was 200 mg mm-2 day-1 × 3. The dose-limiting toxicity was myelosuppression. Discussion. Etoposide given by 72-h infusion is inactive as second-line chemotherapy in STS. It is associated with significant toxicity when given in these doses, in this patient group.

Case report: Bilateral recurrent tension pneumothorax complicating combination chemotherapy for soft tissue sarcoma

Case report: Bilateral recurrent tension pneumothorax complicating combination chemotherapy for soft tissue sarcoma

856 Intensified adjuvant chemotherapy for extremity soft tissue sarcomas (STS)

Adjuvant chemotherapy for STS still remains a matter of debate, since just few randomized studies have indicated a small advantage in terms of disease free interval or overall survival at preliminary reports. However, the majority of those trials have not included adequate doses of anthracyclines nor the today most active agent Ifosfamide (IFO). To re-evaluate the role of adjuvant chemotherapy in extremity STS, we started in June ‘92, a co-operative randomized prospective adjuvant study comparing a control arm to an intensified chemotherapy arm. Treatment consisted of Epirubicin 60 mg/m2, day 1&2, Ifosfamide 1.8 g/m2 × 5days as 1 hr infusion, MESNA 60% of the daily IFO dose fractionated in 3 separated doses, fluids 1.5–2.0 litres/day and G–CSF 300 μg/day from + 8 to + 15; treatment was scheduled every 3 weeks for a total of 5 cycles. Of the 37 up to now randomized pts to the chemotherapy arm, 25 are evaluable (5 cycles completed + two months follow-up) for the toxicity and dose intensity evaluation purpose (12 pts not yet evaluable). The median nadir of WBC and PLTS was 1300/μ1 (range: 200–8000/μ1); and, 120000/μ1 (range: 10000–250000/μ1), respectively. Overall, a G4 leukopenia and thrombocytopenia was noted in 30% and 5% of cycles respectively. Anemia progressively worsened and the median HB fall from basal values to the nadir of the 5th cycle was of 4 g/dl (range 0–9.8 g/dl); in 12 of 25 pts (48%) PRBC transfusions were given to prevent symptoms from anemia. Nevertheless, an optimal recovery to pre-treatment values was obtained after 2 months from end of treatment (median HB 13.5; range: 12.7–14.8). Neutropenic fever was observed in 15% of the cycles, prophylactic antibiotics were administered in further 3% of cycles. No pts received pits support. The median average received dose intensity (ARDI) was of 91% (range: 67–100%) and 19/25 pts (76%) received an ARDI > 80%. Causes of reduction in dose intensity were delay in retreatment in 24 cycles and reduction of the dose in 40 cycles. Even through the toxicity was substantial (anemia and leukopenia) it was possible to give an adequate dose intensity to the majority of pts. All but one pt (3 cycles received) completed the forseen 5 cycles employing the predefined dose reduction schema.

Phase II studies of docetaxel in the treatment of various solid tumours

Docetaxel has been evaluated in six tumour types in a total of 189 patients entered into phase II studies. Treatment consisted of a 1 h intravenous infusion of docetaxel 100 mg/m2 repeated every 3 weeks. No premedication was administered for possible hypersensitivity reactions. Docetaxel was found to be effective as first-line chemotherapy for head and neck cancer (response rate 44%) gastric cancer (23%) and melanoma (14%) and as second-line chemotherapy for soft tissue sarcomas (21%; 95% confidence interval: 7.5%-43.7%). The results in colorectal and renal cancer were disappointing, with response rates of less than 10%. The most frequent adverse effects were alopecia (81%), grade III-IV leukocytopenia of short duration (66%) and skin reactions (52%). Hypersensitivity reactions were mild and occurred in 26% of patients. Docetaxel is an important new drug in the treatment of solid tumours.

Systemic Adjuvant Chemotherapy for Soft Tissue Sarcomas

Adjuvant chemotherapy for soft tissue sarcoma remains investigational. Continued study of multidisciplinary treatment programs in high-grade sarcomas in formal clinical trials remains a priority. The National Cancer Institute is currently conducting a randomized trial of postoperative adjuvant doxorubicin and ifosfamide as compared with observation in high-grade sarcoma. The completion and outcome of this trial will contribute to this ongoing debate. Finally, a better understanding of the biology of soft tissue sarcoma that determines subsequent clinical course may serve as a foundation for further investigation.

Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials

Fifteen published randomised trials comparing adjuvant chemotherapy with no chemotherapy in soft-tissue sarcoma (STS) were identified (1546 patients). A qualitative review and a meta-analysis of this published literature were performed. With the qualitative review it was not possible to synthesise the apparently conflicting results of individual trials. The meta-analysis of the published data suggests an improvement in survival at 2 years (OR = 0.73, 95% CI = 0.53-0.99, P = 0.044) and at 5 years (OR = 0.59, 95% CI = 0.45-0.78, P = 0.0002) in favour of chemotherapy. However, the assumptions and approximations required to conduct this quantitative summary demand that the results are interpreted with caution. The only reliable means of assessing the current evidence on whether adjuvant chemotherapy has a role in the treatment of patients with STS, is to collect, check and reanalyse individual patients data (IPD) from each trial centrally, and formally combine the results in a stratified time-to-event analysis. Such an IPD analysis is currently being undertaken by an international collaborative group.

Adjuvant chemotherapy of soft tissue sarcomas in North America.

Questions are frequently posed regarding the efficacy and importance of adjuvant chemotherapy for soft tissue sarcomas. The usual questions are whether chemotherapy adds to surgery and radiation in the management of patients with soft-tissue sarcomas and whether adjuvant chemotherapy is indicated in the management of patients with soft tissue sarcomas. This manuscript is intended to demonstrate that the answer to these questions is yes, but that the questions are, in fact, the wrong questions. I shall review data from a number of North American trials addressing adjuvant chemotherapy of soft tissue sarcomas, a meta-analysis performed by Dr. Zalupski and colleagues at Wayne State University reviewing all adjuvant soft tissue sarcoma studies (Zalupski et al. 1993), and data from studies using preoperative chemotherapy, especially the exciting data of Eilber and colleagues from UCLA (Antman et al. 1989; Kampe et al. 1993).

Multidisciplinary Treatment of Soft Tissue Sarcomas

Foreword to the Series. Preface. List of Abbreviations. 1. Pathology and Grading of Soft Tissue Sarcomas J.M. Coindre. 2. Cytogenetics J.A. Fletcher. 3. Molecular-Biological Studies on Soft Tissue Sarcomas C. Cooper, J. Clark. 4. Diagnostic Imaging K. Herrlin, H. Petterson. 5. Surgical Wound Healing D.S. Springfield. 6. Preoperative Radiation Therapy for Patients with Sarcoma of the Soft Tissues H.D. Suit, I. Spiro. 7. Changing Concepts in the Systemic Treatment of Locally Advanced or Metastatic Soft Tissue Sarcomas J. Verweij, H.M. Pinedo. 8. Adjuvant Chemotherapy of Soft Tissue Sarcomas W.C. Mertens, V.H.C. Bramwell. 9. Preoperative Chemotherapy for Soft Tissue Sarcoma of the Extremities: The Experience at the University of California, Los Angeles C.J. Engel, F.R. Eilber, G. Rosen, M.T. Selch, Yao-Shi Fu. 10. Hyperthermia and Thermochemotherapy R. Issels. 11. Soft Tissue Sarcomas in Children C.B. Pratt, L.E. Kun. Index.

Secondary acute myeloid leukemia as a result of chemotherapy for soft tissue sarcoma

Secondary acute myeloid leukemia as a result of chemotherapy for soft tissue sarcoma

The use of hematological growth factors to enable dose intensification in chemotherapy for soft tissue sarcomas.

The systemic treatment of soft tissue sarcomas is difficult due to the limited availability of active cytotoxic drugs. Combinations of cytotoxic drugs at standard doses do increase toxicity but do not improve response rates or survival. All combinations are limited by myelosuppression, mainly leukocytopenia. For at least two of the four active drugs (doxorubicin and ifosfamide) studies have shown a clear dose-response relationship. Recent studies have focused on increasing dose-intensity by increasing dosages or shortening treatment intervals, which is only possible by the use of hematological growth factors. This review will focus on the latter concept.

Systemic Adjuvant Chemotherapy for Soft Tissue Sarcomas of the Extremities

Adjuvant chemotherapy for the treatment of adult soft tissue sarcomas remains investigational. Review of the previously conducted randomized trials suggests benefits for the use of immediate adjuvant therapy. Precepts for future trials should include selection of patients with a poor prognosis, an emphasis on early institution of dose-intensive combination chemotherapy, and a description of biologic parameters likely to be important in clinical outcomes.

The role of systemic chemotherapy in multimodality therapy of soft tissue sarcoma

Background In spite of effective local treatment, i.e. surgery alone or surgery combined with radiotherapy, the overall prognosis of soft tissue sarcomas is poor. This is caused by the high likelihood of later occurring metastatic disease which is almost never curable. Thus, an effective systemic therapy which can eradicate microscopic metastases early on in the disease is highly warranted. Methods The literature has been reviewed with respect to studies on adjuvant chemotherapy in soft tissue sarcoma. Results Only randomized studies with a no treatment arm can lead to meaningful conclusions. Overall, these studies, using either single agent doxorubicin or doxorubin-based combination chemotherapy, did not result in improved overall survival. Some studies indicated a reduction in local recurrence. Conclusions Based on the results, the routine application of adjuvant chemotherapy in soft tissue sarcoma can presently not be justified. Currently, trials are exploring combinations of agents which are the most effective in metastatic disease. Also, neo-adjuvant chemotherapy trials are being conducted. It is anticipated that in the near future chemotherapy will be combined with hematopoietic growth factors to allow for intensification of the therapy.

Randomized phase II study of neoadjuvant chemotherapy in soft tissue sarcomas in adults. Protocol 62874

Randomized phase II study of neoadjuvant chemotherapy in soft tissue sarcomas in adults. Protocol 62874

軟部悪性腫ようの治療成績

軟部悪性腫ようの治療成績

Chemotherapy of Soft Tissue Sarcomas in the Extremities

A retrospective study on chemotherapy against soft-tissue sarcomas in the extremities was carried out on 98 patients. The local recurrence rate was 10.3% with intensive chemotherapy in post-1980 patients with high-grade sarcomas but 46.7% without chemotherapy--a fairly significant difference (P less than 0.01). The survival rate was significantly higher with intensive chemotherapy in post-1980 patients with high-grade sarcomas. Thus, intensive chemotherapy based on a new protocol should be given in cases of high-grade sarcoma. Considering surgical margin, the local recurrence rate was 33.3% in post-1980 cases inadequately operated upon but 8.6% in those adequately operated upon, which shows a significant difference (P less than 0.05).