CAPecItabine and Tarceva in Advanced Lung Cancer (CAPITAL)

• Research type

  Research Study

• Full title

  CAPecItabine and Tarceva in Advanced Lung Cancer (CAPITAL)

• Contact name

• Sponsor organisation

  Royal Marsden Hospital

• Eudract number

  2008-007317-79

• ISRCTN Number

  n/a

• Research summary

  Effective treatments for patients with advanced non-small cell lung cancer (NSCLC) are lacking. The drug erlotinib (also called Tarceva) has proven activity in NSCLC. The drug capecitabine (also called Xeloda) has proven activity in the treatment of gastrointestinal and breast cancers. Both of these drugs are in tablet form. One of the main mechanisms of action of capecitabine is by inhibiting a protein called thymidylate synthase (TS). Other TS inhibitors have proven activity in the subtype of NSCLC called adenocarcinomas (in the case of pemetrexed). We are researching combining these two drugs: capeticabine and erlotinib in patients with advanced NSCLC of adenocarcinoma sub-type. These two drugs have been combined in patients with cancer of the pancreas, and the side effect profile is acceptable. We are therefore investigating what is the safest dose of capecitabine and erlotinib when taken together, and what are the side-effects caused by taking these two drugs together, in patients with advanced NSCLC.

  Lay Summary of Results:

  Results: Forty patients were recruited, and 1 patient had an EGFR mutation. Dose escalation stopped at capecitabine 1000 mg/m(2) with expansion to 6 patients due to unpredicted DLTs in 2/6 patients: G2 creatinine rise, G2 anaemia, G3 atrial fibrillation and G3 pneumonia. MTD was capecitabine 750 mg/m(2). First-line dose escalation at the MTD led to unpredicted DLTs in 3/4 patients (G3 troponin rise, G2 rash and G2 hyperbilirubinaemia). MTD expansion in the second-line setting was well tolerated. The most common drug toxicities were gastrointestinal (35 %), followed by skin disorders (28 %). The response rate was 3 % with a disease control rate of 34 %. Median progressive-free survival was 1.6 months (95 % CI 1.4-3.5), and median overall survival was 6.1 months (95 % CI 5.1-10.1).

  Conclusion: The MTD for the combination of capecitabine and erlotinib is 750 mg/m(2) BD, 14/21 days, and 100 mg daily, respectively, which is lower than predicted. Capecitabine did not improve the efficacy of erlotinib in aNSCLC unselected for EGFR mutation.

  Keywords: Adenocarcinoma; Capecitabine; Erlotinib; Non-small cell lung cancer; Phase 1.

  Published at https://pubmed.ncbi.nlm.nih.gov/26706729/

• REC name

  London - Surrey Borders Research Ethics Committee

• REC reference

  09/H0806/52

• Date of REC Opinion

  16 Oct 2009

• REC opinion

  Further Information Favourable Opinion