This Article Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Einhorn, L. H. Search for Related Content PubMed Articles by Einhorn, L. H.

Gemzar (Gemcitabine): How I Use It

Indiana University, 550 University Boulevard, University Hospital, Room 1730, Indianapolis, IN 46202-5250

Gemcitabine is a nucleoside analog related to Ara-C. However, compared to Ara-C, it has substantial activity in multiple solid tumors. It has greater cell membrane permeability and longer intracellular retention.

Numerous doses and schedules were evaluated in early phase I-II trials. Slight alterations in schedule caused major alterations in toxicity and efficacy. At the present time, standard doses are 1,000 to 1,250 mg/m² as a 30-min infusion weekly x 3 every four weeks. In pancreatic cancer, the phase III study that led to FDA approval utilized 1,000 mg/m² x seven weeks, one week of rest, and then 1,000 mg/m² weekly x 3 every four weeks. Chemotherapy with gemcitabine is very well tolerated, with minimal myelosuppression, nausea, myalgias, edema, and rash.

Gemcitabine was recently approved by the FDA on the basis of a phase III study in symptomatic pancreatic cancer patients. One hundred twenty-six patients randomized to gemcitabine versus 5-FU (600 mg/m²/week). Clinical benefit response (pain reduction, improved KPS or weight gain) was prospectively evaluated as the primary study endpoint, with values of 23.8% (gemcitabine) versus 4.8% (p = 0.002). In addition, there was a statistically significant survival advantage for gemcitabine, including a one-year survival of 18% versus 2%. Gemcitabine was also evaluated in a separate phase II study in patients with prior 5-FU, and 17 of 63 (27%) had a clinical benefit response.

Gemcitabine is one of the most studied single agents in NSCLC, and worldwide has a reproducible response rate of 20% with only minimal toxicity. A recently published phase I dose escalation study was conducted at M.D. Anderson. The authors demonstrated tolerability of 2,400 mg/m²/weeks (three of four weeks) in NSCLC. It is unknown whether there is any advantage to this "double dose" gemcitabine.

Numerous phase II trials have evaluated the logical combination of cisplatin + gemcitabine in NSCLC. There is preclinical evidence of synergism.

There are several interesting studies in NSCLC. The CALGB will evaluate cisplatin + gemcitabine with XRT. There is potent radiation sensitization, requiring attenuated doses of gemcitabine if given concurrently. ECOG is conducting a phase III study of cisplatin + paclitaxel or docetaxel, CBDCA + paclitaxel, or cisplatin + gemcitabine.

Gemcitabine has significant activity in numerous other solid tumors, including impressive activity in bladder cancer, ovarian cancer, and breast cancer.

Non-cisplatin (or XRT) combinations are considered investigational. At Indiana University, phase I trials of weekly paclitaxel + weekly gemcitabine are currently being conducted.

This Article Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Einhorn, L. H. Search for Related Content PubMed Articles by Einhorn, L. H.