Randomised phase 3 trial of dose dense ICE chemotherapy versus standard ICE in good prognosis small cell lung cancer (SCLC)

Reviewer: S. Jack Wei, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 2, 2003

Presenter: P Lorigan
Presenter's Affiliation: Manchester Lung Cancer Group
Type of Session: Scientific


    Although SCLC is chemosensitive, it is associated with low rates of cure. Several previous phase II and III trials have attempted to increase dose intensity in an attempt to improve the outcome of these patients. Recently the EORTC has reported a trial of dose-dense ACE (doxorubicin, cyclophosphamide, etoposide) chemotherapy that did not result in improvment in overall survival (OS). However, this regimen lacked a platinum-based drug, which is the standard of care for treatment of SCLC in the US. This study examines the effects of dose intensification of a platinum-based regimen for good prognosis SCLC.

Materials and Methods

  • Patients with SCLC who were limited to 1 adverse prognositic factor including extensive stage disease, KPS<60, and abnormal blood chemistries were eligible.
  • Patients were randomized to 2 arms: 1) 6 cycles of ICE (ifosfamide 5 g/m2, carboplatin 300 mg/m2, etoposide 180 mg/m2 on day 1&2) every 4 weeks (S arm) or 2) the same chemotherapy every 2 weeks (DD arm)
  • Patients on the DD arm also received filgrastim and autologous blood transfusions with each cycle.
  • No dose reductions were allowed for adverse reactions; however delays in treatment were allowed. If a patient in the DD arm underwent a delay of >14 days, that patient was switched to the S arm.
  • Sequential thoracic radiation (TRT) was recommended for patients with limited stage disease and prophylactic cranial irradiation (PCI)was recommended for those with a complete response


  • 318 patients were randomized.
  • A total of 18 patients crossed over from the DD arm to the S arm due to treatment delays.
  • More patients on the DD arm received TRT and PCI (156 and 84 patients vs. 121 and 55 patients)
  • A similar number of patients completed all 6 cycles of chemotherapy (69% for S vs. 68% for DD)
  • There was no statistically significant difference in overall response rate between the 2 arms (80% for S vs. 88% for DD, p=0.09).
  • There was no difference between the 2 arms with regards to 2 year OS or time to progression (TTP) (22% and 10.8 mo for S, 19% and 10.7 mo for DD)
  • Patients on the S arm experienced a higher rate of neutropenic sepsis (63% vs. 47%, p=0.001); however patients on the DD arm had a higher rate of other toxicities (37% vs. 53%, p=0.001).
  • Median time free from therapy until disease progression was longer for the DD arm (306 days vs. 224 days).

Author's Conclusions

  • Dose dense ICE chemotherapy was generally well tolerated.
  • There was no improvement in OS or TTP with DD ICE despite the higher rates of TRT and PCI in the DD arm.
  • The 2 yr OS of this trial are similar to other trials employing ICE-V chemotherapy
  • The 2 yr OS for the DD chemotherapy is similar to the recent EORTC trial of DD ACE which also did not show a survival advantage.

Clinical/Scientific Implications

    Despite the use of platinum-based chemotherapy, dose intensification did not result in improved outcome in these patients. The results of this trial combined with the results of the recent EORTC trial provide strong evidence that dose intensification is unlikely to result in significant improvements in the treatment of SCLC. The poor long-term results in the treatment of SCLC warrants further study of alternative treatment regimens and techniques.

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