Seminars in oncology
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Seminars in oncology · Dec 1995
Clinical TrialPhase I/II study of paclitaxel plus cisplatin as first-line chemotherapy for advanced non-small cell lung cancer: preliminary results.
From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). ⋯ In conclusion, at these doses of paclitaxel and cisplatin, the dose-limiting neurologic toxicity is dose dependent and cumulative after a total paclitaxel dose of approximately 1,300 mg/m2. This combination is highly active, with a total objective response rate of 38% and an objective response rate of 47% at paclitaxel doses of 200 mg/m2 or higher. Further evaluation is warranted.
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Seminars in oncology · Dec 1995
Multicenter Study Clinical TrialDocetaxel (Taxotere): an overview of first-line monotherapy.
Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has demonstrated significant activity in five phase II studies as first-line chemotherapy in the treatment of metastatic breast cancer. Overall response rates range from 55.3% to 67.7%, with responses seen at all sites of disease, including lung (40%) and liver (60%). The median duration of response was 8.3 months, and the median duration of survival was 16.4 months. ⋯ The level of activity as a single agent is comparable to that of most anthracycline and non-anthracycline combination chemotherapy regimens. Its activity does not appear to be affected by prior adjuvant chemotherapy. Further studies are ongoing to incorporate docetaxel in combination chemotherapy regimens.
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Seminars in oncology · Dec 1995
Comparative Study Clinical TrialChemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antineoplastic activity against different tumor types, notably ovarian and breast carcinoma. Two phase II trials of 24-hour paclitaxel infusions in chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer (NSCLC) reported response rates of 21% and 24%. Leukopenia was dose limiting: as many as 62.5% of patients experienced grade 4 leukopenia. ⋯ Nausea and vomiting were infrequent, with 14% of patients experiencing grade 1 or 2 and only 2% experiencing grade 3 or 4. Paclitaxel is thus an active single agent in this patient population, with a 3-hour infusion proving comparably effective to a 24-hour infusion and superior in terms of the incidence of hematologic and nonhematologic toxicity. Further phase II studies with paclitaxel combined with other drugs active against NSCLC are indicated, and phase III studies comparing paclitaxel with standard chemotherapy remain to be completed.
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Seminars in oncology · Dec 1995
Clinical TrialPaclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer.
In a phase I study to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin administered every 21 days to women with advanced ovarian cancer, paclitaxel doses were escalated as follows: level 1, 135 mg/m2; level 2, 160 mg/m2; level 3, 185 mg/m2; and level 4,210 mg/m2. The fixed dose of carboplatin at levels 1 through 4 was given to achieve an area under the concentration-time curve (AUC) of 5 using the Calvert formula. In levels 5 and 6 the carboplatin dose was targeted at AUCs of 6 and 7.5, respectively, combined with a fixed paclitaxel dose of 185 mg/m2. ⋯ No patient had disease progression. We conclude that the combination of paclitaxel 185 mg/m2 administered as a 3-hour infusion followed immediately by a 1-hour infusion of carboplatin at an AUC of 6 can be administered safely in a 21-day schedule in the outpatient setting. The recommended dose for phase III studies is paclitaxel 185 mg/m2 and carboplatin AUC 6.
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Seminars in oncology · Oct 1995
Clinical TrialA clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer.
We have developed a regimen incorporating multiple cycles of high-dose carboplatin and fixed-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with granulocyte colony-stimulating factor and peripheral blood stem cell support given every 21 days for up to four cycles. Our phase I study of this regimen has treated 26 patients with good performance status and histologically documented unresectable or metastatic carcinoma, sarcoma, or melanoma, 21 of whom received all planned courses every 21 days. Paclitaxel 250 mg/m2 was infused over 24 hours, followed by a 1-hour carboplatin infusion, with doses escalated between area under the concentration-time curve (AUC) targets of 8 and 20. ⋯ Among 25 evaluable patients, preliminary results show one complete response (ovarian cancer) and 11 partial responses, including four in patients with non-small cell lung cancer. Additional issues to be addressed include the effect of a shorter (or longer) paclitaxel infusion on the carboplatin AUC (and the incidence of toxicity) and whether the discrepancy between actual and predicted AUCs (greater in our study than reported elsewhere) is due to the variability of creatinine clearance-determined glomerular filtration rate or to altered carboplatin pharmacokinetics when a short high-dose infusion follows paclitaxel. Additional patients are being accrued at the AUC of 18.