Ifosfamide and mitomycin in combination for the treatment of patients with progressive advanced non-small cell lung cancer

Campos, E S De; Kamthan, A; Thatcher, Nicholas

doi:10.1016/0277-5379(91)90218-3

Cited by 10 publications

(5 citation statements)

References 11 publications

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“…The worse toxicity profile observed in our series could be tentatively explained with various hypotheses: (1) it may be schedule dependent (3 vs. 1 or 5 infusion days); (2) it may be related to prior treatment extent, since 80% of our patients had received a 4-drug combination as first-line therapy and 35% of patients had received second-line chemotherapy as well, or (3) it may be disease specific. In fact, the subset of pretreated non-small cell lung cancer patients who received MI combination as salvage therapy also presented a lower toxicity with respect to our series (20% of grade 3–4 neutropenia and 0% of anemia and thrombocytopenia) [16]. Conversely, a lower rate of grade 3–4 nausea or vomiting was observed in our population (5 vs. 19–44%).…”

Section: Discussionmentioning

confidence: 54%

“…The planned dose intensity in the current trial with mitomycin at 2 mg/m 2 /week versus 2–2.5 mg/m 2 /week [16,17,18] and ifosfamide at 1.87 g/m 2 /week versus 1.6–2.5 g/m 2 /week [16,17,18] was comparable. Even so, we observed a higher rate of grade 3–4 neutropenia (80 vs. 0–21%), thrombocytopenia (20 vs. 0–15%) and anemia (10 vs. 0%).…”

Section: Discussionmentioning

confidence: 91%

“…This combination therapy had been previously explored in the treatment of advanced non-small cell lung cancer [16,17,18] using ifosfamide at 1.5–1.8 g/m 2 on days 1–5 [16,17] or 5 g/m 2 on day 1 [18] and mitomycin at 1.2 mg/m 2 on days 1–5 [16] or 6–10 mg/m 2 for 1 day [17,18] every 3 [16,18] or 4 weeks [17]. The planned dose intensity in the current trial with mitomycin at 2 mg/m 2 /week versus 2–2.5 mg/m 2 /week [16,17,18] and ifosfamide at 1.87 g/m 2 /week versus 1.6–2.5 g/m 2 /week [16,17,18] was comparable.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of mitomycin and ifosfamide (MI) has been assessed in non-small cell lung cancer yielding an interesting tumor control, and thus, suggesting a possible synergistic activity [16,17,18]. …”

Section: Introductionmentioning

confidence: 99%

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Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial

Cereda¹,

Reni²,

Rognone³

et al. 2011

Chemotherapy

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Background: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. Methods: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m² on day 1, ifosfamide 2,500 mg/m² and mesna 3,000 mg/m² on days 1–3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrolment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. Results: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. Conclusion: Based on the poor outcome observed and on the high level of grade 3–4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial

Cereda¹,

Reni²,

Rognone³

et al. 2011

Chemotherapy

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“…Several studies have shown that changes in the doses and schedules of widely used regimens might lead to improved efficacy and tolerability ( Gurney et al , 1991 ; van Warmerdam et al , 1997 ; Freyer et al , 2001 ; Moore et al , 2006 ). Could this be the case for SCLC regimens?…”

mentioning

confidence: 99%

Mathematical optimisation of the cisplatin plus etoposide combination for managing extensive-stage small-cell lung cancer patients

2017

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Background:Small-cell lung cancer (SCLC) represents one of the most aggressive forms of lung cancer. Despite the fair sensitivity of SCLC to chemotherapy and radiotherapy, the current standard treatment regimens have modest survival rates and are associated with potential life-threatening adverse events. Therefore, research into new optimised regimens that increase drug efficacy while respecting toxicity constraints is of primary importance.Methods:A PK/PD model for the combination of cisplatin and etoposide to treat extensive-stage SCLC patients was generated. The model takes into consideration both the efficacy of the drugs and their haematological toxicity. Using optimisation techniques, the model can be used to propose new regimens.Results:Three new regimens with varying timing for combining cisplatin and etoposide have been generated that respect haematological toxicity constraints and achieve better or similar tumour regression. The proposed regimens are: (1) Protocol OP1: etoposide 80 mg m−2 over 1 h D1, followed by a long infusion 12 h later (over 3 days) of 160 mg m−2 plus cisplatin 80 mg m−2 over 1 h D1, D1–D1 21 days; (2) Protocol OP2: etoposide 80 mg m−2 over 1 h D1, followed by a long infusion 12 h later (over 4 days) of 300 mg m−2 plus cisplatin 100 mg m−2 over 1 h D1, D1–D1 21 days; and (3) Protocol OP3: etoposide 40 mg m−2 over 1 h, followed by a long infusion 6 h later (3 days) of 105 mg m−2 plus cisplatin 50 mg m−2 over 1 h, D1–D1 14 days.Conclusions:Mathematical modelling can help optimise the design of new cisplatin plus etoposide regimens for managing extensive-stage SCLC patients.

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Chemotherapy in Advanced Non-Small Cell Lung Cancer. Changes in Performance Status and Tumour-Related Symptoms

Thatcher

Ranson

Anderson

1994

Innovative Antimetabolites in Solid Tumours

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Ifosfamide and mitomycin in combination for the treatment of patients with progressive advanced non-small cell lung cancer

Cited by 10 publications

References 11 publications

Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial

Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial

Mathematical optimisation of the cisplatin plus etoposide combination for managing extensive-stage small-cell lung cancer patients

Chemotherapy in Advanced Non-Small Cell Lung Cancer. Changes in Performance Status and Tumour-Related Symptoms

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