Ifosfamide, mitomycin and radiotherapy in non-small-cell lung cancer

Chetiyawardana, Shan; Cullen, Michael; Joshi, Rohit; Woodroffe, C.M.

doi:10.1007/bf00263128

Cited by 5 publications

(7 citation statements)

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“…Mitomycin, ifosfamide and cis-platin have been associated with response rates of 20%, 26% and 20% respectively and are the 3 most active agents (Bakowski et al, 1983). We have combined ifosfamide with mitomycin in a recent phase 2 study in NSCLC (Chetiyawardana et al, 1985). Thirty patients were assessable for response to chemotherapy -8 achieving partial remission (PR) and 5 complete remission (CR).…”

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confidence: 99%

Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare

Joshi²,

et al. 1988

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Summary Mitomycin, ifosfamide and cis-platin are three of the most active single agents in the chemotherapy of non-small cell lung cancer. We have combined them for a phase 2 study in patients with inoperable non-small cell lung cancer. The regimen ('MIC') comprised: mitomycin 6mg m -2, ifosfamide 3gm-2 and cis-platin 50mgm-2, with routine use of lorazepam, dexamethasone and high dose metoclopramide for anti-emesis. Seventy-four ambulatory patients with untreated, limited (LD) or extensive (ED) disease have entered this study, and 66 are evaluable for response. Thirty patients (45%) have achieved partial remission and 7 (11%) complete remission, as assessed radiologically. The overall response rate is thus 56% (95% confidence interval 44%-68%). There have been 29/43 responses in LD (67%, 95% CI 53%-81%) and 8/23 in ED (35%, 95% CI 15%-55%). The median response duration, measured from the start of treatment is 8.75 months. The median survival for the whole group is 9.2 months. The principal toxicity was nausea and vomiting which was severe or prolonged (>48h) for one or more courses, in 9% of patients. Performance status (PS) and weight were assessed before, and 3 weeks after the last course of chemotherapy. Fifteen (of 31 evaluable) responders improved their PS and only 1 responder deteriorated. Twenty-one of the 28 evaluable non-responders had no change in PS. The difference in PS change between responders and non-responders is highly significant (P=0.002). Thirty evaluable responders experienced a mean increase in weight of 2.9% with treatment, whereas 24 evaluable non-responders had a mean weight loss of 3.8%. This change is also highly significant (P=0.0013). MIC is clearly a well tolerated regime and among the most active combinations in non-small cell lung cancer. It will now be tested in a randomized trial against no chemotherapy.Non-small cell lung cancer (NSCLC) is the commonest malignant disease in the western world and is among the most chemoresistant. There are only 5 drugs (ifosfamide, mitomycin, cis-platin, vinblastine and vindesine) which, when tested as single agents in large numbers, produce major responses in 15% or more of cases (Kris et al., 1985). Mitomycin, ifosfamide and cis-platin have been associated with response rates of 20%, 26% and 20% respectively and are the 3 most active agents (Bakowski et al., 1983). We have combined ifosfamide with mitomycin in a recent phase 2 study in NSCLC (Chetiyawardana et al., 1985). Thirty patients were assessable for response to chemotherapy -8 achieving partial remission (PR) and 5 complete remission (CR). The overall response rate to chemotherapy was thus 43%. Cis-platin and ifosfamide have demonstrated synergism in experimental models (Goldin, 1982). Although both agents are associated with severe nausea and vomiting, a trial of anti-emetic therapy in our unit suggested that the combination of high dose metoclopramide infusion, lorazepam and dexamethasone would allow these drugs to be combined with acceptable subjective toxicity (O'Brien et al., 1987...

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confidence: 99%

Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare

Joshi²,

et al. 1988

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“…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%

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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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“…However, ifosfamide is one of the most effective cytostatic drugs in the monochemotherapy of NSCLC with remission rates of more than 25% [12,13]. Moreover, there is no indication from the literature that ifosfamide leads to an increased lung toxicity in combination with radiotherapy [14][15][16]. The latter two strong arguments justify the clinical evaluation of ifosfamide in the combined treatment of stage III NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Concurrent Radiochemotherapy with Ifosfamide in Unresectable Stage III Non-Small-Cell Lung Cancer

Schraube¹,

Latz²,

Manegold³

et al. 1998

Oncol Res Treat

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Ifosfamide, mitomycin and radiotherapy in non-small-cell lung cancer

Cited by 5 publications

References 4 publications

Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare

Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare

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

Concurrent Radiochemotherapy with Ifosfamide in Unresectable Stage III Non-Small-Cell Lung Cancer

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