These protocol doses are derived from the carboplatin and intravenous etoposide protocol. Evidence to support the equivalence of oral and intravenous etoposide with a 2:1 dose conversion factor comes from a randomised controlled trial reported by Johnson et al 1991 of cisplatin etoposide. This study is underpowered to justify equivalence for routine care, but suggests this is a reasonable regimen if circumstances preclude intravenous therapy.r
Between July 1986 and December 1988, 83 previously untreated patients with either limited or extensive small cell lung cancer (SCLC) were randomly assigned to one of the two treatment arms: intravenous (IV) group (cisplatin 100 mg/m2 IV day 1 and etoposide 120 mg/m2 IV days 1, 2, and 3, 41 patients), or Oral group (cisplatin 100 mg/m2 IV day 1 and etoposide 120 mg/m2 IV day 1 and 240 mg/m2 orally days 2 and 3, 42 patients).Limited disease patients constituted 49% and 52% of the patients entered into the IV and oral groups, respectively. Treatment was repeated every 4 weeks for a maximum of 6 courses. The primary end points were response, duration of response, time to progression, and survival.
Platinum based regimens are the cornerstone of treatment for small cell lung cancer. Although the majority of published trials utilise the cisplatin-etoposide combination, most patients are treated with carboplatin-etoposide. This is due to the improved tolerability of carboplatin over cisplatin, especially in patients with poor performance status, and the palliative nature of therapy. A meta-analysis of individualised patient data from 4 randomised trials comparing cisplatin-based treatment (n= 328, number of patients with extensive disease= 221) with carboplatin-based treatments (n= 335, number of patients with extensive disease= 232) for first line therapy in small cell lung cancer was reported in 2012. Doses and treatment regimens differed between the trials, and 1 trial administered thoracic radiation therapy for patients with extensive disease.r
© J Clin Oncol 2012
Efficacy
Results showed that the overall response rates (CR + PR) were similar between oral and IV regimens. The median response duration, time to progression, and survival were not significantly different for either dosage schedule.r
Outcomer
|
Oral treatment arm |
IV Treatment arm |
p-value |
LD %(n=22) |
ED %(n=20) |
LD % (n=20) |
ED %(n=21) |
LD |
ED |
Complete Response n(%)
95% CI |
3 (14%)
0-28% |
2 (10%)
0-23% |
2 (10%)
0-23% |
1 (5%)
0 - 14% |
|
5 (12%)
2% - 22% |
3 (7%)
0 - 15 % |
- |
Complete Response + Partial Response n(%)
95% CI |
12 (55%)
34%- 76% |
9 (45%)
23%- 67% |
10 (55%)
33%- 77% |
13 (62%)
41%- 83% |
0.997 |
0.284 |
21 (50%)
35% - 65% |
25 (59%)
44% - 74% |
0.438 |
Stable disease n(%) |
4 (18%) |
6 (30%) |
8 (40%) |
5 (24%) |
- |
10 (24%) |
10 (24%) |
- |
Median duration of response (range) |
6.1 months (0.4+ -18.0) |
6.9 months (1.1+ -13.2) |
- |
Median time to progression |
- |
3.8 months |
- |
6.6 months |
- |
0.437 |
5.9 months |
6.6 months |
0.704 |
Median survival |
10.1 months |
7.0 months |
9.0 months |
8.1 months |
0.500 |
0.587 |
Median overall survival from the COCIS meta-analysis was equivalent in patients receiving cisplatin-based therapy compared with carboplatin-based therapy (9.6 months vs 9.4 months respectively; HR 1.08 and 95% CI 0.92-1.27; p= 0.37), as was median progression free survival (5.5 vs 5.3 months; HR 1.1 and 95% CI 0.94-1.29; p= 0.25), and response rate (67.1 vs 66%; RR 0.98 and 95% CI 0.84-1.16, p= 0.83).r
© J Clin Oncol 2012
Toxicity
In the randomised trial comparing oral and IV etoposide in combination with cisplatin for SCLC, grade 3 or 4 haematologic toxicity (anaemia, thrombocytopenia, and neutropenia) was experienced by 59% of the patients receiving each regimen during the first course and more than 80% of the patients overall. No differences in incidence or degree of neutropenia or thrombocytopenia were noted. However, septic episodes in neutropenic patients occurred in one patient in the oral arm compared with five patients in the IV arm. Moderate to severe anaemia occurred in 12% of the IV-treated patients compared with none in the oral treatment arm (P = 0.025). Otherwise, the toxicity profile was similar and included alopecia, nausea, and vomiting.r
Based on the meta-analysis of the cisplatin-based regimens compared with carboplatin-based regimens, statistically significantly more haematological toxicities (anaemia, thrombocytopenia, leucopenia) were observed in patients treated with carboplatin. Other toxicities (nausea, neurotoxicity, nephrotoxicity) were significantly more common in patients treated with cisplatin.r
© J Clin Oncol 2012