Epirubicin and ifosfamide in advanced soft tissue sarcomas

Frustaci, S.; Foladore, S.; Buonadonna, Angela; Paoli, Antonino De; Crivellari, Diana; Carbone, Antonino; Sorio, Roberto; Morassut, Sandro; Monfardini, S.

doi:10.1093/oxfordjournals.annonc.a058622

Cited by 30 publications

(17 citation statements)

References 10 publications

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“…Imatinib is a potent inhibitor of KIT signaling tyrosine kinase inhibitor (5,6,10,20,29) . Before the use of imatinib, the median survival of the patients with resectable disease was 66 months (5,9) and 9 to 12 months in irresectable disease (3,4,9,11,12,14,38) .…”

Section: Introductionmentioning

confidence: 99%

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Neves¹,

Oshima²,

Neto³

et al. 2009

Arq. Gastroenterol.

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-Context -Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Cellular proliferation and apoptosis is gaining importance for predicting prognosis in several cancers. Objective -To investigate the Ki67 and p53 immunostaining in GISTs. Methods -Specimens from 40 patients with GIST were assessed for immunohistochemical expression of Ki67 and p53. The tumors were divided according the risk of recurrence in two groups: I with high or intermediate risk and; II with low or very low risk. Results -Among the 40 patients, 21 were men, the mean age was 56 years, 16 occurred in the small intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from group II. Half of the patients developed recurrence, being 90% of the group I (P = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level 0.12). This index was marginally higher in the group I patients with recurrence (P = 0.09) compared to the patients of the same group without recurrence. p53 staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67 had been found in the group I tumors when compared to the other group (P = 0.022; OR = 8.00 -IC 95%: 1.32-48.65). Conclusion -The most common site was the small intestine and 80% had a malignant potential justifying the high recurrence observed. No significant correlation was found between p53 and overall outcome of the patients. In group I patients, the evaluation Ki67LI may be a marker of prognosis. The positivity of both markers is higher among the patients with worst prognosis than in the others. HEADINGS -Gastrointestinal stromal tumors. Ki-67 antigen. Tumor suppressor protein p53.

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Section: Introductionmentioning

confidence: 99%

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Neves¹,

Oshima²,

Neto³

et al. 2009

Arq. Gastroenterol.

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“…The anthracyclines doxorubicin and epirubicin (EPI), and the oxazaphosphorine analog of cyclophosphamide, ifosfamide (IFO), have been widely used in the front-line treatment of advanced sarcomas in view of their well known antitumor activity, and response rates up to 40% have been reported with the combination of them [1][2][3]. EPI doses in the range of 75-140 mg/m 2 every 3 weeks in combination with IFO doses in the range of 6-12 g/m2 have been adopted in concurrent administration schedules [4,5].…”

Section: Introductionmentioning

confidence: 99%

Ifosfamide and Epirubicin Combination in Untreated Sarcomas: Two Treatment Schedules

Serrone

Zeuli

Papaldo³

et al. 2001

Oncol Res Treat

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Background : The Epirubicin (EPI) and ifosfamide (IFO) combination has been widely tested in soft tissue sarcomas, even though the optimal schedule of drug administration has still to be defined. In this article, we reviewed the activity and the toxicity of two EPI- and IFO-based schedules in newly diagnosed sarcomas. Material and Methods: 22 patients (group A) received a ‘concurrent’ schedule of short-infusion IFO at total dose of 7.5–9 g/m² over 5 days plus iv bolus EPI at 90–120 mg/m²/cycle, repeated every 3 weeks. The other 22 patients (group B) received a ‘sequential’ schedule of dose-intense, continuous infusion IFO at a total dose of 14–18 g/m² for 2 cycles followed by bimonthly EPI at 120–160 mg/m²/cycle. Application of growth factors was planned for each course of treatment. Results: Since 1994, 44 consecutive patients have been treated. The overall response rate was 35% with no significant differences between the two treatment groups in terms of response rate (group A: 33%, group B: 37%), time to progression (group A: 7 months, group B: 8 months), and overall survival (group A: 12 months, group B: 15 months). General tolerance to treatment was better in group A. Gastrointestinal symptoms occurred significantly more often with the sequential regimen. Severe hematologic toxicity was common but no toxic deaths were observed. Conclusions: Based on this limited experience, a concurrent schedule of EPI and IFO seems to be an appropriate management strategy in the front-line therapy of advanced sarcomas. Nevertheless, a randomized trial is warranted to define the optimal dosages to be used for further clinical trials.

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“…The objective response rate of 30% is clearly inferior to response rates reported from recent phase II studies with high dose ADM/IFO and comparable to the results of CYVADIC, standard-dose ADM/IFO or high-dose singleagent ADM [4,5,7,8,10,12,13,19], Hematological G-CSF was administered only in 8/35 patients with severe neutropenia. It was demonstrated that 7/8 patients could be referred to the next treatment cycle without toxicityrelated delay.…”

Section: Discussionmentioning

confidence: 43%

“…Metastatic soft tissue sarcoma requires systemic treat ment in the majority of patients, although single cases of successful salvage treatment by surgical metastasectomy are reported [3], A widely varying single-agent activity of 5-30% due to the heterogeneity of histological subtypes of soft tissue sarcoma in children and adults was reported for Adriamycin (ADM), ifosfamide (IFO), ctoposide, dacar bazine (DTIC) and cisplatin (DDP) [4][5][6][7][8]. Response rates were further improved using different combination che motherapy regimens [4-6, 8, 9], Combination IFO, ADM and DTIC resulted in a response rate of 49% including 10% complete remissions (CR) [10].…”

Section: Introductionmentioning

confidence: 99%

Combination of 5-Fluorouracil, Adriamycin, Ifosfamide and Cisplatin in Metastatic Adult Soft Tissue Sarcoma: Results of a Phase II Study

Jäger

Klein²,

Wächter³

et al. 1996

Oncology

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Treatment results of advanced soft tissue sarcomas are still suboptimal. To evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5-fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study was initiated in patients with advanced soft tissue sarcomas of different histological subtypes. Fifty-six previously untreated patients with advanced soft tissue sarcomas of different histological subtypes (24 females, 31 males, median age 51.3 years, median Karnofsky performance status 80%) were included in this study. Treatment consisted of ADM 50 mg/m² i.v. on day 1, IFO 4,000 mg/m² i.v. on day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO administration, FU 500 mg/m² i.v. as 24-hour infusion on days 1 + 2, DDP 100 mg/m² i.v. on day 2. This regimen was repeated every 4 weeks for at least 2 cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56 patients. One toxic death due to severe neutropenia and fungal pneumonia occurred. Granulocyte colony-stimulating factor was administered in 8/35 neutropenic patients. Time to recovery was significantly reduced and no infectious complication was observed. WHO grade III/IV toxic diarrhea was observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with ondansetron alone. The overall response rate was 30.3%. The median duration of response (complete/partial response, CR/PR) was 18.1 months, the median progression-free interval was 4.5 months. The median survival time of all patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor-related pain was effectively reduced in 15/31 patients under treatment. FADIP produces comparable response rates to other standard treatment regimens in soft tissue sarcomas. Prolonged duration of response and median survival may be due to the use of continuous infusion of FU as a synergistic factor to alkylating agents. Granulocyte colony-stimulating factor is effective in reducing the otherwise observed high rate of WHO grade III/IV hematological toxicity with severe neutropenia.

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Epirubicin and ifosfamide in advanced soft tissue sarcomas

Abstract: This combination proved to be feasible and tolerable. The overall response rate does not appear to be superior to those with other standard treatments, but it should be pointed out that our patient population was totally unselected.

Cited by 30 publications

References 10 publications

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Ifosfamide and Epirubicin Combination in Untreated Sarcomas: Two Treatment Schedules

Combination of 5-Fluorouracil, Adriamycin, Ifosfamide and Cisplatin in Metastatic Adult Soft Tissue Sarcoma: Results of a Phase II Study

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