Combination Chemotherapy with Irinotecan and Ifosfamide as Second-Line Treatment of Refractory or Sensitive Relapsed Small Cell Lung Cancer: A Phase II Study

Abstract

This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as second-line chemotherapy for relapsed small cell lung cancer (SCLC). Eligibility criteria included histologically or cytologically confirmed SCLC, prior chemotherapy including platinum + etoposide, and measurable or evaluable disease. CPT-11 (80 mg/m²) was administered intravenously on days 1, 8 and 15, while ifosfamide (1.5 g/m²) was given on days 1 through 3 every 4 weeks. Thirty-four patients (29 men) with a median age of 69 years (range 42–77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0–2) were enrolled. The response rate was 52.9% (95% confidence interval: 29.8–64.9%) with 2 complete responses and 16 partial responses. Our analyses of prognostic factors showed risk factors assessed before receiving second-line chemotherapy, which were the number of metastatic sites, performance status and the type of relapse. WHO grade 3–4 neutropenia was recorded in 52.9% of the patients, grade 3 diarrhea in 5.9%. The combination of CPT-11 and ifosfamide demonstrated clinical efficacy in relapsed SCLC with a favorable toxicity profile, particularly for performance status 0–1 and sensitive cases with only one metastatic site.

The cytogenetic action of ifosfamide, mesna, and their combination on peripheral rabbit lymphocytes: an in vivo/in vitro cytogenetic study

“…However, in spite of its successful anticancer action, the increased toxicity presented in healthy tissues and particularly in the renal and the bladder epithelium, led to its restricted usage and administration. This pressing issue was overcome with the development of mesna acting in an antioxidant fashion, was proven to successfully protect from the running risk of emergence of hemorrhagic cystitis as well as from other side effects of IFO (Anderson 2010;Ichiki et al 2003;Olver et al 2005). IFO is a well known and widely applied anticancer substance but it also has cytotoxic effects.…”

A Phase I Study of Prolonged Ambulatory Infusion of Ifosfamide with Oral Mesna

“…Most studies suggest great inter-patient variation in the pharmacokinetics [8] . On a 5-day infusional schedule, Cerny et al [8] reported that the optimal dose in pretreated patients was 12-14 g/m 2 , and further dose escalation did not add therapeutic benefi t but increased toxicity. However, high doses (often defi ned as over 10 mg/m 2 ) may circumvent the resistance to standard doses [20] .…”

“…Ifosfamide, an analogue of cyclophosphamide, is an alkylating agent currently in use for the treatment of a variety of tumours including germ cell tumors, lung cancer and sarcomas [1][2][3] . It is a prodrug which is initially metabolized by P450 to therapeutically active and potentially toxic metabolites [4] .…”

“…They recommended a dose of 500 mg/m 2 /day resulting in a cumulative dose of 7.0 g/m 2 , which approximates the optimal single-agent doses of 5-8 g/m 2 . Without mesna, microscopic haematuria was seen at doses of 400 mg/m 2 /day and above in this 14-day ambulatory infusion schedule.…”

P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11

“…The cytotoxic activity of CPT-11 has been reported in several malignant tumors, including breast, lung, ovarian, and colon cancer (9)(10)(11)(12)(13)(14)(15)(16). CPT-11 serving as a DNA topoisomerase I inhibitor, combined with 5-fluorouracil (5-FU) and leucovorin has been accepted as a first-line treatment for patients with advanced CRC.…”