Meta-analysis of ifosfamide-based combination chemotherapy in advanced soft tissue sarcoma.

BACKGROUND: This meta-analysis examines the role of ifosfamide-based combination chemotherapy in patients with advanced soft tissue sarcoma. Outcomes of interest include overall survival, response rate, adverse effects, and quality of life. METHODS: A systematic review of the literature was searched to identify relevant articles. RESULTS: Three randomized phase III trials were identified comparing combination chemotherapy regimens containing ifosfamide with regimens without ifosfamide. Two randomized trials demonstrated that the addition of ifosfamide to either doxorubicin or to a regimen of doxorubicin and dacarbazine, significantly improved response rates. One randomized trial reported a significant improvement in overall survival for patients receiving doxorubicin and dacarbazine compared to those receiving a combination of doxorubicin, dacarbazine, and ifosfamide (MAID). A meta-analysis of these studies revealed that the addition of ifosfamide to a chemotherapy regimen significantly improves the tumour response rate (RR, 1.52, p=0.009) but does not produce a significant difference in 1-year survival (RR, 0.98, p=0.76). Higher rates of adverse events, particularly grades 3-4 myelosuppression, were observed in patients who received regimens that contained ifosfamide. A higher rate of toxic deaths was reported in two of the three trials, for the ifosfamide containing regimen. Data on quality of life were not reported. CONCLUSION: In patients with metastatic soft tissue sarcoma, the routine addition of ifosfamide to standard first line doxorubicin-containing regimens is not recommended over single agent doxorubicin. However, it may be reasonable to employ such combinations in patients with symptomatic, locally-advanced, or inoperable soft tissue sarcoma where response might render such tumours resectable.

Dose-intensive chemotherapy with growth factor or autologous bone marrow/stem cell transplant support in first-line treatment of advanced or metastatic adult soft tissue sarcoma: a systematic review.

A systematic review was performed to determine whether first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation improves response rate, time-to-disease progression, or survival compared with standard-dose chemotherapy in patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. The MEDLINE, EMBASE, and Cochrane Library databases were searched. Three randomized trials (2 phase 3, 1 phase 2), 12 phase 2, and 5 phase 1 dose-escalation trials were located. One randomized trial (N=314) did not detect significant differences in response rate (P=.65) or survival (log-rank P=.98) between high-dose doxorubicin plus ifosfamide with granulocyte macrophage colony-stimulating factor and doxorubicin plus ifosfamide at standard doses. Progression-free survival, however, was significantly longer in the high-dose arm (log-rank P=.03). Higher rates of thrombocytopenia, infection, grade 3 of 4 asthenia, and stomatitis were observed with high-dose compared with standard-dose chemotherapy. Preliminary results from a second randomized trial (N=162) indicated no benefit with respect to tumor response for an intensified mesna, doxorubicin (Adriamycin), ifosfamide, and dacarbazine regimen with granulocyte colony-stimulating factor support compared with standard doxorubicin, ifosfamide, and dacarbazine. Grade 4 thrombocytopenia was significantly higher with the high-dose regimen. Four phase 2 trials of high-dose regimens observed tumor response rates greater than 50%. Phase 1 trials reported dose-limiting toxicity for dose-intensive chemotherapy regimens. On the basis of the available evidence, high-dose chemotherapy with growth factor or autologous bone marrow/stem cell transplantation should not be used in the routine treatment of patients with inoperable, locally advanced, or metastatic soft tissue sarcoma.

Chemotherapy for relapsed small cell lung cancer: a systematic review and practice guideline.

PURPOSE: This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC). METHODS: Relevant randomized trials and meta-analyses were identified through a systematic search of the literature. External feedback was obtained from practitioners in Ontario, and the guideline was approved by the provincial lung cancer disease site group. RESULTS: Six randomized trials met the eligibility criteria and were included for review. One randomized phase III trial of oral topotecan versus no treatment in patients receiving best supportive care found topotecan to have a significant benefit in terms of 6-month survival and quality of life. A randomized phase III trial compared outcomes of carboplatin in patients receiving a combination of etoposide and cisplatin (EP) and found no significant improvement associated with carboplatin, although it was associated with significantly higher grade 3/4 thrombocytopenia. Two randomized trials directly compared chemotherapy regimens (intravenous [i.v.] topotecan versus cyclophosphamide, doxorubicin, and vincristine (CAV); and bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC) versus EP), but these trials found no significant differences in terms of disease response or survival. I.v. topotecan was associated with significantly higher toxicities (grade 4 thrombocytopenia and grade 3/4 anemia) and greater improvement in patient-reported symptoms compared with CAV. Two randomized trials of topotecan-treated patients comparing route of administration (i.v. versus oral) found no significant differences in terms of disease response, survival, or quality of life, although oral administration was associated with increased grade 3 or 4 diarrhea in both trials. CONCLUSION: Evidence on the clinical benefit of second-line therapy in SCLC is limited. Topotecan is the most studied agent in this population; it has a response and survival benefit in comparison with placebo, but it also has greater toxicity in comparison with CAV. To date, significant differences in terms of response and survival are not evident in studied chemotherapy options.

The role of high-dose-rate brachytherapy in the palliation of symptoms in patients with non-small-cell lung cancer: a systematic review.

PURPOSE: This review addresses the role of high-dose-rate endobronchial brachytherapy (HDREB) for symptom palliation in patients with non-small-cell lung cancer. METHODS AND MATERIALS: Relevant trials were identified through a systematic search of the literature. RESULTS: Twenty-nine trials were eligible. Six randomized trials involved HDREB alone or with external beam radiation therapy (EBR) or laser therapy. Median and 1-year survival ranged from 4 to 10 months and from 11% to 38%, respectively. Symptoms controlled by HDREB were dyspnea, cough, chest pain, and hemoptysis. Fatal hemoptysis ranged from 7% to 22%. Better overall symptom palliation and fewer retreatments were required in previously untreated patients using EBR alone or EBR with HDREB. CONCLUSIONS: EBR alone is more effective than HDREB for symptom palliation in previously untreated patients with endobronchial non-small-cell lung cancer. HDREB with EBR seems to provide better symptom relief than EBR alone. HDREB is recommended for symptomatic patients with recurrent endobronchial obstruction previously treated by EBR, providing it is technically feasible.

The role of radiation therapy in malignant pleural mesothelioma: a systematic review.

INTRODUCTION: Radiation therapy may offer patients presenting with malignant pleural mesothelioma (MPM) symptom palliation and improvements in quality of life. This systematic review will address the role of radiation therapy in the management of MPM. METHODS: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials were selected and assessed. RESULTS: Three small randomized controlled trials compared prophylactic external beam radiation therapy to no radiation therapy for patients with thoracic tracts caused by drainage tubes or diagnostic procedures. None of those trials reported any serious adverse effects. A pooled analysis found no significant reduction in the frequency of procedure tract metastases. Four non-comparative studies have shown that hemithoracic irradiation alone resulted in significant toxicity, including radiation-induced pulmonary fibrosis, radiation pneumonitis, and bronchopleural fistula, without any survival benefit. Few of the identified studies reported on symptom control, and no studies included formal measures of quality of life. CONCLUSION: There is limited evidence for the role of radiotherapy in the management of patients with MPM. Future studies including radiotherapy for the treatment of such patients should include formal measures of quality of life and symptom control.