The evidence supporting this treatment comes from large randomised trial, by von Pawel et al comparing CAV (cyclophosphamide, adriamycin and vincristine) with single agent topotecan administered as 3 weekly cycles. In this trial 211 patients with relapsed small cell lung cancer who had completed first line therapy at least 60 days before were randomised to either CAV or topotecan, in patients experiencing an objective response, therapy was continued until disease progression or unacceptable toxicity occurred, or for at least 6 courses past the maximal response. The majority (about 80%) of patients had been treated with etoposide and a platinum agent. The primary efficacy parameters were response rate and duration of response. Secondary efficacy parameters were time to progression, time to response, survival and improvement of disease related symptoms.r
This study showed that toxicity with both regimens was high and toxicity was overall equivalent. Issues in choosing a preferred regimen include the cost and overall tolerability. Clinical experience is that many oncologists prefer topotecan because the (predominately haematological) toxicity is better tolerated. Cost is greater with topotecan and it is not PBS subsidised.
Response rate was 26 out of 107 patients (24.3%, all partial responses) with topotecan and 19 out of 104 (18.3%, 1% complete responses) with CAV (P=.285).
Median times to progression were 13.3 weeks topotecan and 12.3 weeks CAV (P=.552).
Median survival duration was 25.0 weeks with topotecan and 24.7 weeks with CAV(P=.795).
Topotecan was shown to be as effective as CAV and was more effective than CAV for palliation of symptoms, including dyspnoea, anorexia, hoarseness, fatigue, and interference with daily activity.r
|Time to progression
|| 25 weeks
© J Clin Oncol 1999
The toxicity below is based on a 5 day regimen.r
Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anaemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Non hematologic toxicities were generally grade 1 to 2 for both regimens.
|| Topotecan Grade 3-4
|CAV Grade 3-4