Phase II Study of Paclitaxel, Ifosfamide, and Cisplatin  as Second-Line Treatment in Relapsed Small-Cell  Lung Cancer

Kosmas, Christos; Tsavaris, Nicolas; Malamos, Nikolaos; Vadiaka, Maria; Koufos, Christos

doi:10.1200/jco.2001.19.1.119

Cited by 61 publications

(34 citation statements)

References 24 publications

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“…Toxicity in the CIP arm was greater than reported elsewhere; however, the phase I dose-escalating study (Papadimitriou et al, 2001) used prophylactic G-CSF and had febrile neutropaenia in one patient out of eight treated at doses comparable with ours, and the phase II trial (Kosmas et al, 2001) reported less frequent highgrade haematological toxicity but used only 1.5 g m À2 ifosfamide, which is 70% lower than the dose we used. Overall, the results of this study indicate low feasibility of the CIP regimen with a starting dose of 5 g m À2 ifosfamide, at least without prophylactic G-CSF.…”

Section: Discussioncontrasting

confidence: 47%

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A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis

et al. 2008

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To test the feasibility and efficacy of epirubicin and ifosfamide added to first-line chemotherapy with cisplatin and paclitaxel in a phase II randomised clinical trial. Patients with histologically proven epithelial ovarian cancer were randomly assigned to receive firstline polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP) or cisplatin/paclitaxel/ifosfamide (CIP) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms and the median number of cycles per patient was six. Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm. Response rates were 85% (95% confidence interval (CI) 77 -93%) in the CIP arm and 90% (95% CI 84 -96%) in the CEP arm; complete response rates were 48 and 52%. After a median follow-up of 82 months, median overall survival (OS) was 51 and 65 months; 5-year survival rates were respectively 43 and 50%. In this clinical trial, both regimens showed good efficacy, but toxicity was heavier with the CIP regimen. Considering that more than 50% of patients were suboptimally debulked after the first surgery, OS seems to be longer than is commonly reported. This unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach.

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Section: Discussioncontrasting

confidence: 47%

“…Shortly after the start of this clinical trial, in a phase I and a phase II trial of cisplatin and paclitaxel combined with ifosfamide, significant activity against ovarian epithelial cancer was noted. The regimen was feasible with ifosfamide doses up to 5 g m À2 (Kosmas et al, 2001;Papadimitriou et al, 2001).…”

mentioning

confidence: 99%

A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis

et al. 2008

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“…One trial where patients were treated with a combination of paclitaxel, cisplatin, and ifosfamide showed a response rate of 70%. Although the median survival of the platinum-resistant patients was not reported separately, the median survival of all patients treated (20 with platinum resistant and 13 with platinum sensitive disease) was 7 months (40).…”

Section: Discussionmentioning

confidence: 99%

Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer

Antonia

Mirza

Fricke

et al. 2006

Clinical Cancer Research

388

272

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Purpose: The initial goal of this study was to test the immunologic and clinical effects of a new cancer vaccine consisting of dendritic cells (DC) transduced with the full-length wild-type p53 gene delivered via an adenoviral vector in patients with extensive stage small cell lung cancer. Experimental Design: Twenty-nine patients with extensive stage small cell lung cancer were vaccinated repeatedly at 2-week intervals. Most of the patients received three immunizations. p53-specific responses were evaluated, and phenotype and function of Tcells, DCs, and immature myeloid cells were analyzed and correlated with antigen-specific immune responses. Objective clinical response to vaccination as well as subsequent chemotherapy was evaluated.Results: p53-specificTcell responses to vaccination were observed in 57.1% of patients. Immunologic responses to vaccination were positively associated with a moderate increase in the titer of antiadenovirus antibodies, and negatively with an accumulation of immature myeloid cells. One patient showed a clinical response to vaccination whereas most of the patients had disease progression. However, we observed a high rate of objective clinical responses to chemotherapy (61.9%) that immediately followed vaccination. Clinical response to subsequent chemotherapy was closely associated with induction of immunologic response to vaccination. Conclusions: This study provides clinical support for an emerging paradigm in cancer immunotherapy, wherein optimal use of vaccination might be more effective, not as a separate modality, but in direct combination with chemotherapy.

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“…Based on these preclinical in vitro experimental data, we believe that the sequence and infusion times regarding docetaxel and ifosfamide, as applied in the present study, might lead to potential in vivo synergism between these two drugs (Kearns et al, 1995). Moreover, our prior experience with paclitaxel -ifosfamidecisplatin (Kosmas et al, 2000a, b;2001) or docetaxel -ifosfamide -cisplatin (Kosmas et al, 2002) combinations has demonstrated their feasibility in phase I and phase II studies in advanced solid tumours and lung cancer in particular.…”

Section: Discussionmentioning

confidence: 75%

Phase I–II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer

Kosmas

Tsavaris²,

Malamos

et al. 2003

Br J Cancer

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Given the established individual activity of docetaxel and ifosfamide in anthracycline pretreated advanced breast cancer, the present phase I -II study aimed to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and activity of the docetaxel -ifosfamide combination in this setting. Cohorts of three to six patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel 70 -100 mg m À2 over 1 h on day 1 followed by ifosfamide 5 -6 g m À2 divided over days 1 and 2 (2.5 -3.0 g m À2 day À1 over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. In total, 56 patients with a median age of 54.5 (range, 32 -72) years and performance status (WHO) of 1 (range, 0 -2) were treated at five DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 35 were treated at DL4 (total of 41 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 53 for response. Dose-limiting toxicity (with the addition of G-CSF after DL2) was reached at DL5 with two out of three initial patients developing febrile neutropenia (FN). Clinical response rates, on an intention-to-treat basis, in phase II were: 53.6% (95% CI, 38.3 -68.9%); three complete remissions, 19 partial remissions, seven stable disease, and 12 progressive disease. The median response duration was 7 months (3 -24 months), median time to progression 6.5 month (0.1 -26 month), and median overall survival 13 months (0.1 -33 months). Grade 3/4 toxicities included time to progression neutropenia in 78% of patients -with 63% developing grade 4 neutropenia (p7 days) and in 12% of these FN, while no grade 3/4 thrombocytopenia was observed. Other toxicities included peripheral neuropathy grade 2 only in 12%, grade 1/2 reversible CNS toxicity in 17%, no renal toxicity, grade 2 myalgias in 10%, grade 3 diarrhoea in 10%, skin/nail toxicity in 17%, and grade 2 fluid retention in 2% of patients. One patient in the study treated at phase II died as a result of acute liver failure after the first cycle. In conclusion, the present phase I -II study determined the feasibility of the docetaxel -ifosfamide combination, defined the MTD and demonstrated the encouraging activity of the regimen in phase II, thus warranting further randomised phase III comparisons to singleagent docetaxel or combinations of the latter with other active agents. ) has demonstrated a broad spectrum of activity against a variety of advanced solid tumours, and breast cancer represents the first in which docetaxel has been successfully tested (Salminen et al, 1999). In particular, for patients with prior anthracycline-based therapy, taxanes represent the treatment of choice in the salvage setting, since previously applied agents have demonstrated infe...

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Phase II Study of Paclitaxel, Ifosfamide, and Cisplatin as Second-Line Treatment in Relapsed Small-Cell Lung Cancer

Abstract: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned.

Cited by 61 publications

References 24 publications

A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis

A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis

Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer

Phase I–II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer

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