gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Pemetrexed Combined with Paclitaxel: A Phase I Trial in Advanced Solid Tumors

Meeting Abstract

  • corresponding author presenting/speaker Tobias Graefe - St. Georg Hospital, Hamburg, Deutschland
  • Claus Bolling - St. Georg Hospital, Hamburg
  • Corinna Lübbing - St. Georg Hospital, Hamburg
  • Emine Yilmaz - St. Georg Hospital, Hamburg
  • Sigrun Müller-Hagen - Onkologische Schwerpunktpraxis, Hamburg
  • Bernhard Leisner - St. Georg Hospital, Hamburg
  • Johannes Blatter - Eli Lilly & Company, Indianapolis
  • Axel-Rainer Hanauske - St. Georg Hospital, Hamburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO443

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Graefe et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Pemetrexed (Alimta®, AL) and paclitaxel (P) are clinically active in a variety of tumors. The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) of the ALP combination; secondary objectives included determination of dose-limiting toxicities (DLTs), recommended phase II dose, and pharmacokinetic (PK) assessments.

Methods: Escalating dose levels of P (30-120 mg/m2, 3h infusion, d1 and d8) and AL (400-500 mg/m2, 10 min infusion, d8 prior to P) were administered during a 21d cycle. Parenteral vitamin B12, oral folic acid and standard taxane premedication were used to reduce toxicity.

Results: 59 patients (pts) [40 M, 19 F; median age: 59 yrs (range: 31-77)] were enrolled. DLTs, not qualifying for MTD, occurred at the following ALP (mg/m2) doses: 400/30 [1 pt: G3 bilirubin (b), 1 pt: G3 and G4 thrombocytopenia (plts)]; 500/30 (G4 plts); 500/40 (G3 b); 500/75 (G4 ANC); 500/100 (1 pt: G4 leukopenia and G4 ANC). The MTD defined by G4 leukopenia and G4 neutropenia in 4 out of 6 pts and febrile neutropenia in 1 pt, was determined at the ALP (mg/m²) dose of 500/120 To confirm safety at this dose-level, 6 more pts were enrolled at a ALP (mg/m²) dose of 500/100.

Other clinically significant toxicities include: G3/G4 ANC (17/14), G3/G4 anemia (6/1), G3/G4 plts (2), G3 fatigue (2) and G3 stomatitis (1). 4 pts expired while on therapy (1 non-therapy related; 1 gastric ulcer hemorrhage, 1 sepsis, 1 tumor lysis and 1 pneumonia). Stable disease occurred in 18 pts [mesothelioma (3), esophagus (2), lung (1), liver (1), renal (1), stomach (1), thyroid (9)]. Of specific relevance, this regimen shows clear clinical activity in follicular/papillary thyroid cancer with 4/14 pts showing long lasting partial responses [duration (months) 34+, 22+, 18, 15+]. At present there is no clinical evidence of PK interactions. Final PK analysis is pending.

Conclusions: The pemetrexed and paclitaxel combination can be safely combined and shows broad clinical activity. The recommended dose for further studies of the ALP combination is 500/100 mg/m². Promising antitumor activity was observed in thyroid cancer. This warrants further clinical development in this indication.