nab-paclitaxel -ABI007 - ABRAXANE

The so much enthusiasm in target agents did not over throw the research in optimizing the currently available and successful chemotherapeutic agents like paclitaxel or Taxol.

Paclitaxel (Taxol) is not water soluble that is why its preparation is cremophor bound compounds to allow more tissue delivery. Scientists have discovered that the cremophor by itself has toxicity and is claimed to be reason behind the allergic and sensitivity reactions to paclitaxel and neuropathy.

The new paclitaxel form is a basically albumin bound in the so called nanoparticle albumin bound form;

nab-paclitaxel -ABI007 - ABRAXANE.

Many advantages of this albumin bound form include:

1. The higher and faster tissue delivery which means the use of same dose with less toxicity and or a tissue delivery of higher doses than conventional.

2. Rapid tissue recovery which means less tissue exposure and toxic

3. Higher tumor tissue selectivity which means less selectivity to blood elements and less neutropenia.

In fact the study lead to approval of nab-paclitaxel (Abraxane or ABI007) has confirmed the proposed advantages.

The study was a phase III study in which metastatic breast cancer patients were randomized between two arms of treatment; one arm is the conventional Paclitaxel (Taxol) at a dose of 175mg/m2/ 3 wks and the study arm wad the nap-paclitaxel at a dose of 260mg/m2/3wks.

The results showed an overall response rate of

33% in the nab-paclitaxel (Abraxane or ABI007) arm compared to

19% in the conventional Paclitaxel (Taxol) arm.

Moreover, patients received the treatments as first line therapy showed a response rate of

42% in the nab-paclitaxel (Abraxane or ABI007) arm compared to

24% in the Paclitaxel (Taxol) arm.

TTP was 23 weeks in the nab-paclitaxel (Abraxane or ABI007) arm compared to

16.9 weeks in the Paclitaxel (Taxol) arm.

Side effects were as expected with less neutropenia and hypersensitivity reactions in the nab-paclitaxel (Abraxane or ABI007)  arm.

Regarding sensory neuropathy which was significantly higher in the nab-paclitaxel (Abraxane or ABI007)  arm, it was easily manageable with fast recovery in 22 days compared to 79 days in the Paclitaxel (Taxol) arm .

All results were statistically significant.

In a randomized Phase 2 Study of different doses of Weekly nab-Paclitaxel Versus Every-3- week Docetaxel as First-line Therapy in Patients with Metastatic Breast Cancer as follows:

nab-Paclitaxel 150 mg/m2 weekly 3 out of 4

nab-Paclitaxel 300 mg/m2 weekly 3 out of 4

nab-Paclitaxel 100 mg/m2 weekly 3 out of 4

Docetaxel 100 mg/m2 q3w

The study showed better response rate and toxicity profile with the dose  of nab-Paclitaxel 100 mg/m2 . Objective response rate of 58% least toxicity in terms of neutropenia and sensory neuropathy.

Promising results that encouraged many ongoing trials replacing the conventional Paclitaxel (Taxol).

References:

O’Shaughnessy, et al., SABCS. 2003.

   Gradishar W, et al December 14–17, 2006; San Antonio, Tex. Abstract 46.