- Email: [email protected]
Can chemosensitivity testing predict response to chemotherapy regimens in non-small cell lung cancer?
Chemotherapy/Paclitaxel pharmacokinetics and estimated interpatient variability of CYP3A4 activity applying our method was assessed. Results: After cortisol administration, the total amount of 24-hour urinary 6 6-OHF (T6 6-OHF) increased about 60-fold compared with pretreatment levels averaging 12,273 +/- 4,076 (SD) ix g/day. Docetaxel clearance (CL) and area under the concentration-time curve averaged 24.5 +/- 6.4 L/h/m2 and 2.66 +/- 0.91 mg/L • h, respectively. An excellent correlation between docetaxel CL and T6 6-OHF was observed (r = 0.867). In multivariate analysis, T613-OHF (p < 0.001), alpha 1-acid glycoprotein (p = 0.004), serum aspartate aminotransferase (p = 0.007) and age (p = 0.022) significantly correlated with docetaxel CL. Conclusion: The interpatient variability of CYP3A4 activity and docetaxel CL could be predicted by measuring T613-OHF after cortisol administration.
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chemosensitivity testing predict response to chemotherapy regimens in non-small cell lung cancer?
M. Kawamura, T. Abiko, M. Gika, K. Kobayashi. School of Medicine,
Keio University, Tokyo, Japan Objective: We examined the applicability of a new type of in vitro chemosensitivity assay, collagen gel droplet embedded culture drug sensitivity testing (CDDST), to evaluation of chemotherapy regimens for non-small cell lung cancer. Methods: The new assay can assess chemosensitivity using a small number of tumor cells such as those obtained by biopsy. Results: Seventy percent of all specimens examined were evaluable using this method. Bronchoscopic biopsy specimens were evaluable in 37.8% of cases. This lower evaluability rate was chiefly due to an insufficient number of tumor cells included in the specimen. In vitro-in vivo correlation with CDDST was, assessed in 41 patients with measurable non-small cell lung cancer lesions. The true positive rate was 84.6%. The true negative rate was 100%. Sensitivity and specificity was 100% and 66.7%, respectively. Among 175 patients with non-small cell lung cancer, 75 (42.9%) had no effective anticancer drug regimen according to the new assay. Conclusion: Our data show that CDDST are clinically useful for chemosensitivity testing.
Wednesday, 13 S e p t e m b e r 2000
10:30-12:00
ORAL SESSION
Chemotherapy/Paclitaxel
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Phase II study with gemcitabine and paclitaxel administered once every two weeks in chemonaive advanced stage non-small cell lung cancer (NSCLC) patients
C. Fontaine 1, (3. Joos2, J. De Gr(~ve1, J. De MeyI , R. Van Klaveren3, B. Neyns 1, V. Van de Velde2, I. Stappaerts 3, P. Pinson 4, D. Grauwels 5, J. Van Hulle 5, D. Schallier~. 1AZ-VUB Brussels; 2Ghent University
Hospital; 3UZ Antwerp; 4For Eli Lilly Brussels; 5Bristol-Myers Squibb, Belgium Background: Both gemcitabine (Gemzar~) and paclitaxel (Taxol~)) have significant activity in NSCLC. Initial phase I studies with the onceevery-two-week schedule have recommended doses of 3000 mg/m2 of gemcitabine and 150 mg/m 2 of paclitaxel for phase II studies. Eligibility: Chemonaive histologically proven NSCLC pts, stage IIIB/IV, PS 0-2 (ECOG), at least one measurable lesion. Results: Patient characteristics: 32 patients (pts) were eligible for this study (7 stage IlIB - 25 stage IV; 29 male - 3 female; 14 adenocarcinoma - 9 squamous cell - 2 large cell - 7 other; median age 58 years; PS 0 (9), 1 (20), 2 (3)).
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Activity: One hundred thirty-seven (137) cycles were administered (median 6; range 1 to 9). Six pts were not evaluable for activity due to early discontinuation of therapy: 3 hypersensitivity reactions, 1 diminished CO diffusion capacity, 2 early deaths. Of 26 pts. evaluable for response, which was peer reviewed, 9 achieved a partial response (35%). On intent-to-treat basis a response rate of 28% was achieved. Median time to progression and median survival were 2.9+ months and 4.8+ months respectively (10 patients being still alive at the time of the present analysis). Toxicity (NCI CTC Gr 3-4; worst toxicity per cycle): Hematologic toxicity: neutropenia 5%; non-hematoiogic toxicity: dyspnea 4%; fever 3%; neuropathy 3%; fatigue 3%; cardiac 3%; liver (increase of alkaline phosphatase) 2%. Conclusion: The once-every-two-week combination of gemcitabine/paciitaxel which is easy to administer in the out-patient clinic, offers an activity comparable to platinum containing regimens. The level of toxicity (especially myelosuppression) was low in this NSCLC patient population.
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multicenter, phase II study of combination paclitaxellgemcitabine in previously untreated stage IV non-small cell lung (NSCLC) cancer patients
G. Edelman, S. Melville, W. Meyer, S. Napier. US Oncology, Irving,
Texas, USA Introduction: Combination chemotherapy offers many advantages to treating patients with advanced NSCLC. A promising combination may be gemcitabine/paclitaxel (G/P). Objective: To determine the response rate of G/P in chemonaive patients with advanced or metastatic NSCLC. Patients and Methods: We used a regimen based on previous phase I data (Ann Onc 9:733-738, 1998): P 150 rag/m2 IV over 3 hours followed by G 3000 mg/m2 IV over 30 minutes, repeated every 14 days. Two weeks consititued one cycle. Results: 86 patients, 57 (66%) males and 29 (33%) females, entered this trial with a mean age of 63 years (range 40-78). Most were Caucasian (83%) followed by African Americans (9%) and Hispanics (6%); 73% had stage IV, 18% had stage IIIb, and 2% had stage Ilia disease. Histological diagnoses included adenocarcinomas (45%), squamous ceil (20%), large cell (15%) and unknown (20%). Patients received an average of 7 cycles (range 1-23). Primary reasons for discontinuation were disease progression (39%), adverse events (14%), and patient or physician request (14%). Seven patients died during the trial. Of the 63 evaluable patients (received 3 cycles of therapy), the overall response rate was 30% (1 CR and 18 PR); 13 additional patients had stable disease. Mean duration of response was 9.7 months. Mean overall survival was 9.1 months. Grade 3/4 hematologic toxicities included: neutropenia 7%/1%, thrombocytopenia 3%/0%, and anemia 3%/1%. Grade 3/4 nonhematoiogic toxicities included: nausea, asthenia, hyperglycemia, anorexia, hypotension, and dyspnea. There was one case each of grade 3 anaphylaxis and seizure. There were no statistically significant changes between baseline and post-treatment scores in patient-assessed quality of life measured by the FACT-L questionnaire. Conclusion: The combination of G/P is a well-tolerated and effective regimen in the treatment of cheonaive patients with NSCLC. ~ - ] Phase II study of paclitaxel and carboplatin for advanced Non-Small-Cell Lung-Cancer G.V. Scagliotti, S. Novello, L. Crin, S. Ricci, G. Selvaggi, L. Galli, A. Antonuzzo, A.M Mosconi, S. Porrozzi, S. Darwish, M. Tonato.
University of Turin, Orbassano; Medical Oncology Division, Bologna; Medical Oncology Division, Pisa; Medical Oncology Division, Perugia, Department of Clinical and Biological Sciences, Italy After establishing the maximum tolerated doses (Lung Cancer 1999, 25: 39-46) from November 1997 to October 1998 we enrolled 60 previously untreated, histologically proven, stage Illb (n = 15) and IV
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chemosensitivity testing predict response to chemotherapy regimens in non-small cell lung cancer?
M. Kawamura, T. Abiko, M. Gika, K. Kobayashi. School of Medicine,
Keio University, Tokyo, Japan Objective: We examined the applicability of a new type of in vitro chemosensitivity assay, collagen gel droplet embedded culture drug sensitivity testing (CDDST), to evaluation of chemotherapy regimens for non-small cell lung cancer. Methods: The new assay can assess chemosensitivity using a small number of tumor cells such as those obtained by biopsy. Results: Seventy percent of all specimens examined were evaluable using this method. Bronchoscopic biopsy specimens were evaluable in 37.8% of cases. This lower evaluability rate was chiefly due to an insufficient number of tumor cells included in the specimen. In vitro-in vivo correlation with CDDST was, assessed in 41 patients with measurable non-small cell lung cancer lesions. The true positive rate was 84.6%. The true negative rate was 100%. Sensitivity and specificity was 100% and 66.7%, respectively. Among 175 patients with non-small cell lung cancer, 75 (42.9%) had no effective anticancer drug regimen according to the new assay. Conclusion: Our data show that CDDST are clinically useful for chemosensitivity testing.
Wednesday, 13 S e p t e m b e r 2000
10:30-12:00
ORAL SESSION
Chemotherapy/Paclitaxel
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Phase II study with gemcitabine and paclitaxel administered once every two weeks in chemonaive advanced stage non-small cell lung cancer (NSCLC) patients
C. Fontaine 1, (3. Joos2, J. De Gr(~ve1, J. De MeyI , R. Van Klaveren3, B. Neyns 1, V. Van de Velde2, I. Stappaerts 3, P. Pinson 4, D. Grauwels 5, J. Van Hulle 5, D. Schallier~. 1AZ-VUB Brussels; 2Ghent University
Hospital; 3UZ Antwerp; 4For Eli Lilly Brussels; 5Bristol-Myers Squibb, Belgium Background: Both gemcitabine (Gemzar~) and paclitaxel (Taxol~)) have significant activity in NSCLC. Initial phase I studies with the onceevery-two-week schedule have recommended doses of 3000 mg/m2 of gemcitabine and 150 mg/m 2 of paclitaxel for phase II studies. Eligibility: Chemonaive histologically proven NSCLC pts, stage IIIB/IV, PS 0-2 (ECOG), at least one measurable lesion. Results: Patient characteristics: 32 patients (pts) were eligible for this study (7 stage IlIB - 25 stage IV; 29 male - 3 female; 14 adenocarcinoma - 9 squamous cell - 2 large cell - 7 other; median age 58 years; PS 0 (9), 1 (20), 2 (3)).
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Activity: One hundred thirty-seven (137) cycles were administered (median 6; range 1 to 9). Six pts were not evaluable for activity due to early discontinuation of therapy: 3 hypersensitivity reactions, 1 diminished CO diffusion capacity, 2 early deaths. Of 26 pts. evaluable for response, which was peer reviewed, 9 achieved a partial response (35%). On intent-to-treat basis a response rate of 28% was achieved. Median time to progression and median survival were 2.9+ months and 4.8+ months respectively (10 patients being still alive at the time of the present analysis). Toxicity (NCI CTC Gr 3-4; worst toxicity per cycle): Hematologic toxicity: neutropenia 5%; non-hematoiogic toxicity: dyspnea 4%; fever 3%; neuropathy 3%; fatigue 3%; cardiac 3%; liver (increase of alkaline phosphatase) 2%. Conclusion: The once-every-two-week combination of gemcitabine/paciitaxel which is easy to administer in the out-patient clinic, offers an activity comparable to platinum containing regimens. The level of toxicity (especially myelosuppression) was low in this NSCLC patient population.
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multicenter, phase II study of combination paclitaxellgemcitabine in previously untreated stage IV non-small cell lung (NSCLC) cancer patients
G. Edelman, S. Melville, W. Meyer, S. Napier. US Oncology, Irving,
Texas, USA Introduction: Combination chemotherapy offers many advantages to treating patients with advanced NSCLC. A promising combination may be gemcitabine/paclitaxel (G/P). Objective: To determine the response rate of G/P in chemonaive patients with advanced or metastatic NSCLC. Patients and Methods: We used a regimen based on previous phase I data (Ann Onc 9:733-738, 1998): P 150 rag/m2 IV over 3 hours followed by G 3000 mg/m2 IV over 30 minutes, repeated every 14 days. Two weeks consititued one cycle. Results: 86 patients, 57 (66%) males and 29 (33%) females, entered this trial with a mean age of 63 years (range 40-78). Most were Caucasian (83%) followed by African Americans (9%) and Hispanics (6%); 73% had stage IV, 18% had stage IIIb, and 2% had stage Ilia disease. Histological diagnoses included adenocarcinomas (45%), squamous ceil (20%), large cell (15%) and unknown (20%). Patients received an average of 7 cycles (range 1-23). Primary reasons for discontinuation were disease progression (39%), adverse events (14%), and patient or physician request (14%). Seven patients died during the trial. Of the 63 evaluable patients (received 3 cycles of therapy), the overall response rate was 30% (1 CR and 18 PR); 13 additional patients had stable disease. Mean duration of response was 9.7 months. Mean overall survival was 9.1 months. Grade 3/4 hematologic toxicities included: neutropenia 7%/1%, thrombocytopenia 3%/0%, and anemia 3%/1%. Grade 3/4 nonhematoiogic toxicities included: nausea, asthenia, hyperglycemia, anorexia, hypotension, and dyspnea. There was one case each of grade 3 anaphylaxis and seizure. There were no statistically significant changes between baseline and post-treatment scores in patient-assessed quality of life measured by the FACT-L questionnaire. Conclusion: The combination of G/P is a well-tolerated and effective regimen in the treatment of cheonaive patients with NSCLC. ~ - ] Phase II study of paclitaxel and carboplatin for advanced Non-Small-Cell Lung-Cancer G.V. Scagliotti, S. Novello, L. Crin, S. Ricci, G. Selvaggi, L. Galli, A. Antonuzzo, A.M Mosconi, S. Porrozzi, S. Darwish, M. Tonato.
University of Turin, Orbassano; Medical Oncology Division, Bologna; Medical Oncology Division, Pisa; Medical Oncology Division, Perugia, Department of Clinical and Biological Sciences, Italy After establishing the maximum tolerated doses (Lung Cancer 1999, 25: 39-46) from November 1997 to October 1998 we enrolled 60 previously untreated, histologically proven, stage Illb (n = 15) and IV