- Email: [email protected]
28 Palliative chemotherapy in stage IV NSCLC
Abstracts Not Preuented/Chemothempy: disease in 15 pts (88.2%). Median duration of clinical response was 93 days (range 28-258), survival 137 days (range 54-332). At this writing 12 pts (70.5%) are still alive. Conclusions: Based on these preliminary data 3-day El therapy migth play a role in the future as second line tratment in NSCLC pts recurrent after Platinumcontaining regimens for its favorable safety profile with a mild and reversible myelotoxicity. The antitumor activity in terms of partial response and disease control seems to be acceptable and the median overall survival interesting. In this pattern of pts in second-line chemotherapy we observed a good palliation of NSCLC symptoms mainly for dyspnea and fatigue with an improvement of Quality of Life.
28
Palliative chemotherapy
in stage IV NSCLC
El Gordana D. Radosavlievic-Asic, Dragana Jovanovic, Ljudmila Nagorni, Tatjana Adzic. /n&f&e for Lung diseases, CCS, Be/grade, Serbia
Background: In poor countries, cytostatic treatment is rarely applied in NSCLC - IV st., mostly for the palliative purposes in younger pts and good PS. Material and methods: A prospective study of 59 pts diagnosed in stage IV NSCLC in our institution during the period 2001-02 (31+28 pts). Two platinum-based CT courses were initially applied, followed by assessment of the achieved results and new decision on further treatment. Results: The patients were averagely aged 54 yrs. Patients’ KPS: 70 in 12 (20%) cases, 80 in 24 (41%) and 90 in 23 (39%). Visceral and bone metastases were present in 38 (64%) and 21 (36%) cases, respectively. (CNS metastases were ruled out). The time “lost” between the onset of initial symptoms till establishment of LC diagnosis ranged between 2 and 96 weeks, mediana 8. After two CT courses, PR was found in 11 (19%) cases, SD in 16 (27%) and PD in 32 (54%). Cytostatic treatment was continued in all PR cases till the moment of disease progression, as well as in 4 of 16 (25%) SD cases, while in PD pts, further treatment included only symptomatic drug treatment, mostly using combination of non-steroidal antirheumatic drugs, corticosteroids and anxiolytic. Conclusions: NSCLC diagnosed in its stage IV does not necessarily mean large tumor mass or longer “lost” time, however it does mean more aggressive tumor. In limited health care conditions, application of CT is in such cases highly restrictive and justifiable only from the individual patients’ point of view. Palliative drug treatment of the symptoms is a base of health care of these patients. El29
A phase II trial - Gemcitabine plus carboplatin in advanced non small cell lung cancer (NSCLC): Preliminary results
Jaime E. Rubio, Guillermo Sahagdn, Jorge D. Rodriguez, Francisco Figueroa, Gilbert0 Morgan. lnsfituto Mexicano de/ Seguro Social, Guadalajara, M&ico
Purpose: To analyse, objective response, toxicity, tolerability, time to progression (TTP) and survival. Methods: Since September 2001 all eligible patients, were included and received gemcitabine 1000 mg/m* in days 1 and 8 plus carboplatin 300 mg/m2 day 1, each 28 days, until six cycles, followed by radiotherapy and/or surgery. Results: At the date of the analysis, 29 patients were included, 20 male and 9 female, medium age of 61.37 years, range 40-81; 82.7% smokers. Stage IV 58.6%, stage lllb 37.9% and stage llla 3.4%. 27/29 patients were evaluated for response. The response was observed as follows: Objective response (OR) 29.6%, complete response (CR) 14.8%, and 5 OR > 50% 14.8%. 29.6% with OR i 50%, 25.9% with no change (NC), and 14.8% with progression. The Control Tumour Rate (OR+PR<50%+NC) was 85.1%. Toxicity was 3 events of mild dermatitis. Grade 3: only 1 episode of vomits, 1 in platelets and 2 patients with alopecia. Grade 4; only 1 episode of vomits and 1 in platelets. We can not evaluate TTP and survival yet. No patients were withdrawn from study. Conclusions: This regimen is effective in advanced NSCLC. The toxicity is mild and the scheme was well tolerated. We need more time to analyse TTP and survival. El30
Effects of chemotherapy on lung cancer cell lines measured with Fourier Transform Infrared Spectroscopy
Josep Sul&Suso’ , Vladimir Zholobenko2, Nicholas Stone3, Alicia El Haj’. ’ Keele Universif)! Stoke on Trent, United Kingdom; ‘Keele lJnivers& Stoke on Trent, United Kingdom; 3 Cranfield Postgraduate Medical School, Gloucester, United Kingdom Chemotherapy for non small cell lung cancer is still an area of much debate. It is not clear yet which is the best chemotherapy combination to treat this disease. Therefore, it would be ideal to have a tool that could allow clinicians to predict which chemotherapy drugs would give the highest tumour cell killing. One of these tools could be Fourier Transform Infrared (FTIR) spectroscopy. This technique uses infrared light applied to a sample and measures the vibrational modes of the functional groups of biomolecules in cells and tissues. The
NSCLC 2
S281
frequency of light that is absorbed by a sample depends upon the nature of the bond between the atoms, the atoms involved in the bond, the type of vibration and factors such as the strength of any hydrogen bonding interactions. The amount of light absorbed by a vibrating bond is linearly related to concentration. Therefore, the infrared spectrum of a sample is a direct indicator of its chemical composition. We therefore measured the effects of gemcitabine on in vitro growing lung cancer cells by FTIR spectroscopy. The spectrum of gemcitabine revealed two peaks at 1730 cm-l and 1680 cm-l with a 1730/1680 cm-i ratio greater than 1. The addition of different doses of gemcitabine to in vitro growing lung cancer cell lines CALU-I and SK-MES showed a decrease in the 1680 cm-l peak intensity. However, the decrease of the 1680 cm-i peak intensity was less in the case of lung cancer cell line SKLU-I. The fact that no changes were seen in the 1730 cm-l peak in all three cell lines, would suggests that the decreased intensity at 1680cm-1 in CALU-1 and SK-MES cell lines was due to the drug being metabolised in these cells rather than being removed from the cells. In the case of SKLU-I, the higher intensity at 1680 cm-l when compared to 1730 cm-l would suggest that this cell line is less efficient when metabolising gemcitabine. The applications of FTIR spectroscopy as a tool to monitor the effects of chemotherapy on in vitro growing cancer cells will be discussed.
I31
Second line chemotherapy with docetaxel in elderly advanced NSCLC patients: A phase II study
Carmelo Tibaldi’, llaria Bernardini’, Francesca Russo2, Antonio Chella3, Giovanni Toma4, Fabrizio Tempestinis, Anna Maria Santolicandro5, Alfred0 Falcones. ’Azienda USL 6 Livorno, Livorno, Italy; ‘AZ. USL 6 Livorno, Livorno, ItalK 3 Dip Cardiotoracico Univ. di Piss, Pisa, Italia; 4 AZ. USL 6 Livorno, Livorno, Italia; 5Az USL 6 Livorno, Livorno, Ha/y Rationale: In advanced NSCLC patients previously treated with at least one line of chemotherapy, treatment with Docetaxel at the dose of 75mg/sqm every 3 weeks (dose intensity= 25 mg/sqm/week) is associated with prolongation of survival. Neutropenia is the DLT of this schedule and limits its use in elderly advanced NSCLC patients. In the attempt to improve the compliance to the treatment, but mantaining the same dose intensity of the original regimen, we have performed a phase II study in elderly (age>70 years) advanced NSCLC patients progressed after 1 line of chemotherapy, with the following modified schedule: Docetaxel 37.5 mg/sqm on days 1 and 8 every 3 weeks (planned dose intensity= 25 mg/sqm/week) for a maximum of six courses. Responses were assessed after 3 courses Patients characteristics: up to now 17 patients are enrolled, 14 males and 3 females; median age 73 yrs range (7080). PS: O=l, 1=13, 2=3; 5 pts. were adenocarcinoma, 7 squamous, 4 large cell, 1 NSCLC. Total number of cycles administered are 52 (median 4 cycles); we have observed the following (WHO) hematological and not hematological toxicity (% of the courses):
Neutropenia Thrombocytopenia Anemia
Gi
G2
G3
G4
3.8
-
-
7.7
3.8
-
-
Nausea/vomiting Diarrhea Stomatitis Skin toxicitv
Gl
G2
G3
G4
11.5 13.5
2 3.8
25 3.8
5.8
2 -
-
-
Responses: up to now IO/17 patients are evaluable for response: 1 PR, 6 SD, 3 PD; Conclusions: Second line chemotherapy with Docetaxel administered at the dose of 37.5 mg/sqm iv days. 1,8 every 21 seems to be active and well tolerated with a good compliance in elderly advanced pts. The study is ongoing to better define the activity and toxicity of this regimen.
cl32
A Phase II study of Docetaxel (D) in combination with carboplatin (C) in the treatment of stagelllb and IV non-small cell lung cancer patients
Kostas Pavlos Zaroqoulidis, Athanasios Xafenias, Theodore Kontakiotis, Afrodite Chatzopoulou, Panagiotis Panousis, Dimitris lakovidis. Lung Tumor Researche Section, Pulmonary Clinic, Aristotle University, Thessaloniki, Greece, Thessaloniki, Greece We investigated the efficacy of D in combination with C in the treatment of NSCLC pts. Since 1996, 172 pts with inoperable NSCLC has been enrolled in the study; 171 pts, (149 M, 22 F, median age 60 f 8.5 years) were evaluated. of those, 58 pts had squamous, 74 adenocarcinoma, 13 large cell, 9 bronchoalvealar, IO mixed type and 8 undifferentiated NSCLC. Eligibility criteria induced documented stage lllb and IV NSCLC, WHO PS O-1, age up to 73 years and normal renal and hepatic function. A total of 1089 cycles of chemotherapy (median 6 & 2 courses per patient) were administered. Each cycle consisted of 100 mg/m* of D in a 2-h infusion with C at a dose of AUC 5.5 on Di. Bitamine B6 250 x 3 (x I-14) day in each cycle were administered to prevent neuropathy. These regimens were repeated every 28 days up to eight cycles. Four patients (2.3%) achieved complete response, 63 (36.8%) partial response, 61 (35.6%)
28
Palliative chemotherapy
in stage IV NSCLC
El Gordana D. Radosavlievic-Asic, Dragana Jovanovic, Ljudmila Nagorni, Tatjana Adzic. /n&f&e for Lung diseases, CCS, Be/grade, Serbia
Background: In poor countries, cytostatic treatment is rarely applied in NSCLC - IV st., mostly for the palliative purposes in younger pts and good PS. Material and methods: A prospective study of 59 pts diagnosed in stage IV NSCLC in our institution during the period 2001-02 (31+28 pts). Two platinum-based CT courses were initially applied, followed by assessment of the achieved results and new decision on further treatment. Results: The patients were averagely aged 54 yrs. Patients’ KPS: 70 in 12 (20%) cases, 80 in 24 (41%) and 90 in 23 (39%). Visceral and bone metastases were present in 38 (64%) and 21 (36%) cases, respectively. (CNS metastases were ruled out). The time “lost” between the onset of initial symptoms till establishment of LC diagnosis ranged between 2 and 96 weeks, mediana 8. After two CT courses, PR was found in 11 (19%) cases, SD in 16 (27%) and PD in 32 (54%). Cytostatic treatment was continued in all PR cases till the moment of disease progression, as well as in 4 of 16 (25%) SD cases, while in PD pts, further treatment included only symptomatic drug treatment, mostly using combination of non-steroidal antirheumatic drugs, corticosteroids and anxiolytic. Conclusions: NSCLC diagnosed in its stage IV does not necessarily mean large tumor mass or longer “lost” time, however it does mean more aggressive tumor. In limited health care conditions, application of CT is in such cases highly restrictive and justifiable only from the individual patients’ point of view. Palliative drug treatment of the symptoms is a base of health care of these patients. El29
A phase II trial - Gemcitabine plus carboplatin in advanced non small cell lung cancer (NSCLC): Preliminary results
Jaime E. Rubio, Guillermo Sahagdn, Jorge D. Rodriguez, Francisco Figueroa, Gilbert0 Morgan. lnsfituto Mexicano de/ Seguro Social, Guadalajara, M&ico
Purpose: To analyse, objective response, toxicity, tolerability, time to progression (TTP) and survival. Methods: Since September 2001 all eligible patients, were included and received gemcitabine 1000 mg/m* in days 1 and 8 plus carboplatin 300 mg/m2 day 1, each 28 days, until six cycles, followed by radiotherapy and/or surgery. Results: At the date of the analysis, 29 patients were included, 20 male and 9 female, medium age of 61.37 years, range 40-81; 82.7% smokers. Stage IV 58.6%, stage lllb 37.9% and stage llla 3.4%. 27/29 patients were evaluated for response. The response was observed as follows: Objective response (OR) 29.6%, complete response (CR) 14.8%, and 5 OR > 50% 14.8%. 29.6% with OR i 50%, 25.9% with no change (NC), and 14.8% with progression. The Control Tumour Rate (OR+PR<50%+NC) was 85.1%. Toxicity was 3 events of mild dermatitis. Grade 3: only 1 episode of vomits, 1 in platelets and 2 patients with alopecia. Grade 4; only 1 episode of vomits and 1 in platelets. We can not evaluate TTP and survival yet. No patients were withdrawn from study. Conclusions: This regimen is effective in advanced NSCLC. The toxicity is mild and the scheme was well tolerated. We need more time to analyse TTP and survival. El30
Effects of chemotherapy on lung cancer cell lines measured with Fourier Transform Infrared Spectroscopy
Josep Sul&Suso’ , Vladimir Zholobenko2, Nicholas Stone3, Alicia El Haj’. ’ Keele Universif)! Stoke on Trent, United Kingdom; ‘Keele lJnivers& Stoke on Trent, United Kingdom; 3 Cranfield Postgraduate Medical School, Gloucester, United Kingdom Chemotherapy for non small cell lung cancer is still an area of much debate. It is not clear yet which is the best chemotherapy combination to treat this disease. Therefore, it would be ideal to have a tool that could allow clinicians to predict which chemotherapy drugs would give the highest tumour cell killing. One of these tools could be Fourier Transform Infrared (FTIR) spectroscopy. This technique uses infrared light applied to a sample and measures the vibrational modes of the functional groups of biomolecules in cells and tissues. The
NSCLC 2
S281
frequency of light that is absorbed by a sample depends upon the nature of the bond between the atoms, the atoms involved in the bond, the type of vibration and factors such as the strength of any hydrogen bonding interactions. The amount of light absorbed by a vibrating bond is linearly related to concentration. Therefore, the infrared spectrum of a sample is a direct indicator of its chemical composition. We therefore measured the effects of gemcitabine on in vitro growing lung cancer cells by FTIR spectroscopy. The spectrum of gemcitabine revealed two peaks at 1730 cm-l and 1680 cm-l with a 1730/1680 cm-i ratio greater than 1. The addition of different doses of gemcitabine to in vitro growing lung cancer cell lines CALU-I and SK-MES showed a decrease in the 1680 cm-l peak intensity. However, the decrease of the 1680 cm-i peak intensity was less in the case of lung cancer cell line SKLU-I. The fact that no changes were seen in the 1730 cm-l peak in all three cell lines, would suggests that the decreased intensity at 1680cm-1 in CALU-1 and SK-MES cell lines was due to the drug being metabolised in these cells rather than being removed from the cells. In the case of SKLU-I, the higher intensity at 1680 cm-l when compared to 1730 cm-l would suggest that this cell line is less efficient when metabolising gemcitabine. The applications of FTIR spectroscopy as a tool to monitor the effects of chemotherapy on in vitro growing cancer cells will be discussed.
I31
Second line chemotherapy with docetaxel in elderly advanced NSCLC patients: A phase II study
Carmelo Tibaldi’, llaria Bernardini’, Francesca Russo2, Antonio Chella3, Giovanni Toma4, Fabrizio Tempestinis, Anna Maria Santolicandro5, Alfred0 Falcones. ’Azienda USL 6 Livorno, Livorno, Italy; ‘AZ. USL 6 Livorno, Livorno, ItalK 3 Dip Cardiotoracico Univ. di Piss, Pisa, Italia; 4 AZ. USL 6 Livorno, Livorno, Italia; 5Az USL 6 Livorno, Livorno, Ha/y Rationale: In advanced NSCLC patients previously treated with at least one line of chemotherapy, treatment with Docetaxel at the dose of 75mg/sqm every 3 weeks (dose intensity= 25 mg/sqm/week) is associated with prolongation of survival. Neutropenia is the DLT of this schedule and limits its use in elderly advanced NSCLC patients. In the attempt to improve the compliance to the treatment, but mantaining the same dose intensity of the original regimen, we have performed a phase II study in elderly (age>70 years) advanced NSCLC patients progressed after 1 line of chemotherapy, with the following modified schedule: Docetaxel 37.5 mg/sqm on days 1 and 8 every 3 weeks (planned dose intensity= 25 mg/sqm/week) for a maximum of six courses. Responses were assessed after 3 courses Patients characteristics: up to now 17 patients are enrolled, 14 males and 3 females; median age 73 yrs range (7080). PS: O=l, 1=13, 2=3; 5 pts. were adenocarcinoma, 7 squamous, 4 large cell, 1 NSCLC. Total number of cycles administered are 52 (median 4 cycles); we have observed the following (WHO) hematological and not hematological toxicity (% of the courses):
Neutropenia Thrombocytopenia Anemia
Gi
G2
G3
G4
3.8
-
-
7.7
3.8
-
-
Nausea/vomiting Diarrhea Stomatitis Skin toxicitv
Gl
G2
G3
G4
11.5 13.5
2 3.8
25 3.8
5.8
2 -
-
-
Responses: up to now IO/17 patients are evaluable for response: 1 PR, 6 SD, 3 PD; Conclusions: Second line chemotherapy with Docetaxel administered at the dose of 37.5 mg/sqm iv days. 1,8 every 21 seems to be active and well tolerated with a good compliance in elderly advanced pts. The study is ongoing to better define the activity and toxicity of this regimen.
cl32
A Phase II study of Docetaxel (D) in combination with carboplatin (C) in the treatment of stagelllb and IV non-small cell lung cancer patients
Kostas Pavlos Zaroqoulidis, Athanasios Xafenias, Theodore Kontakiotis, Afrodite Chatzopoulou, Panagiotis Panousis, Dimitris lakovidis. Lung Tumor Researche Section, Pulmonary Clinic, Aristotle University, Thessaloniki, Greece, Thessaloniki, Greece We investigated the efficacy of D in combination with C in the treatment of NSCLC pts. Since 1996, 172 pts with inoperable NSCLC has been enrolled in the study; 171 pts, (149 M, 22 F, median age 60 f 8.5 years) were evaluated. of those, 58 pts had squamous, 74 adenocarcinoma, 13 large cell, 9 bronchoalvealar, IO mixed type and 8 undifferentiated NSCLC. Eligibility criteria induced documented stage lllb and IV NSCLC, WHO PS O-1, age up to 73 years and normal renal and hepatic function. A total of 1089 cycles of chemotherapy (median 6 & 2 courses per patient) were administered. Each cycle consisted of 100 mg/m* of D in a 2-h infusion with C at a dose of AUC 5.5 on Di. Bitamine B6 250 x 3 (x I-14) day in each cycle were administered to prevent neuropathy. These regimens were repeated every 28 days up to eight cycles. Four patients (2.3%) achieved complete response, 63 (36.8%) partial response, 61 (35.6%)