Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study

Abstract

To compare irinotecan (CPT-11) þ gemcitabine vs CPT-11 alone as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) progressing after docetaxel -cisplatinum-based therapy. A total of 147 evaluable, pretreated patients, with NSCLC, received either gemcitabine (1000 mg m À2 , days 1 and 8) þ CPT-11 (300 mg m À2, day 8) (Group A, n ¼ 76) or CPT-11 (300 mg m À2 , day 1) (Group B, n ¼ 71), every 3 weeks. All patients were evaluable for response and toxicity. The objective response rate was 18.4% (95% CI: 9.71 -27.14%) and 4.2% (95% CI: 0 -8.90%) (P ¼ 0.009) for groups A and B, respectively. No significant differences between the two groups in terms of the median duration of response, time to tumour progression, overall survival and 1-year survival were observed. The CPT-11/gemcitabine regimen significantly improved the patients' quality of life ('general mood today' (P ¼ 0.014), 'coughing' (P ¼ 0.003) and 'intensity of symptoms' (P ¼ 0.034)) compared with CPT-11. More cycles had to be delayed (P ¼ 0.001) and required prophylactic growth factor support (P ¼ 0.001) in Group A than B. Three (3.9%) patients in Group A and eight (11.3%) in Group B developed febrile neutropenia (P ¼ 0.09); one patient died of sepsis in each group. Three additional (Group A, n ¼ 1; Group B, n ¼ 2) treatment-related deaths were observed. Grade 3 -4 haematologic toxicity was comparable in the two groups except anaemia (P ¼ 0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and similar in the two groups. CPT-11 þ gemcitabine resulted in a higher response rate and better control of disease-related symptoms than CPT-11 alone, but without any improvement in the overall survival.

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study

“…Similarly, a 31% response rate was observed (Nakanishi et al, 1999) with a weekly administration of irinotecan and cisplatin in 16 patients with refractory NSCLC. A recent multicenter, randomised phase II study, which compared the irinotecan/gemcitabine combination vs irinotecan in NSCLC patients pretreated with taxanes plus cisplatinum, demonstrated a poor antitumour activity of irinotecan (ORR ¼ 4.2%) (Georgoulias et al, 2004) as already reported by Negoro et al (see Ferrigno and Buccheri, 2000). Taken together, the improved antitumour activity of irinotecan/cisplatin combination (Nakanishi et al, 1999;Kakolyris et al, 2001) and the poor activity of single agent irinotecan or cisplatin in the second-line setting seem to indicate an in vivo synergism between the two agents as it has been shown in preclinical studies (Kano et al, 1992;Kudoh et al, 1993).…”

KRAS driven expression signature has prognostic power superior to mutation status in non‐small cell lung cancer

“…TOP1 (topoisomerase 1) plays a crucial role in DNA replication and maintaining genome stability by regulating the supercoiling state of DNA. TOP1 is also the cellular target for irinotecan, an agent approved for advanced or metastatic NSCLC 36. Higher expression of TOP1 in KRAS mutant patients and correlation to survival suggests that TOP1 inhibitors might have increased benefit when administered to treat patients with a KRAS mutant tumor.…”

Phase I study of amrubicin and vinorelbine in non-small cell lung cancer previously treated with platinum-based chemotherapy

“…Several randomized phase II trials have compared combination chemotherapy with monotherapy in the secondline setting. Georgoulias et al 22 compared irinotecan plus gemcitabine with irinotecan alone as a second-line treatment for patients with progression of advanced NSCLC after cisplatin plus docetaxel-based therapy. No signifi cant differences were observed between the groups in time to tumor progression (7.5 months vs 5.0 months) or overall survival (9.0 months vs 7.0 months).…”