- Email: [email protected]
TXT) as second-line treatment in advanced non-small cell lung cancer (NSCLC) patients pretreated with non-platinum-based regimens
Poster Session l/Chemotherapy: nia with no febrile neutropenia, and 3 patients (10%) had grade 3 anemia. Two patients (6%) had grade 3, and 6 patients (19%) grade 1-2 neurotoxicity. Conclusions: The combination of gemcitabine and oxaliplatin seems to be well tolerated and active in patients with poor prognosis advanced NSCLC and deserves further evaluation in phase II clinical trials.
P 40 L-J
Cisplatin and Vinorelbine chemotherapy for stage MB and IV non-small cell lung cancer: an experience from a Chest Diseases Hospital in Turkey
Nilgun Fatma Hatabay, Ferah Ece. SSK Sureyyapasa Chest and Cardiovascular Diseases Hospital, Istanbul-Turkey Istanbul, Turkey
Purpose: to evaluate the efficacy of cisplatin (CDDP) - vinorelbine (VNR) regimen in chemonaive (NSCLC).
patients with stage IlIE - IV nonsmall
cell lung cancer
Patients and Methods: From April 2000 to December 2001, 63 patients with advanced NSCLC were included in the study. Fifty nine patients were male and 4 female, median age was 57 years (37-76) ECOG performans status (PS) O/l was 40/23, stage IIIB/IV was 27/36. Histologic diagnosis was squamous cell lung cancer in 30 patients, adenocarcinoma in 22 and undifferentiated NSCLC in 11. Two patients had curative radiotherapy (RT) before chemotherapy (ChT). None of the patients had curative RT after ChT where as 15 had palliative RT for brain, bone metastases and pain relief. Treatment consisted of 30 mg/ms VNR on days I,8 and 70 mg/ms CDDP on day 1 of every 3 weeks. Results: All patients were evaluated for time to progression and overall response rate and toxicity. Twenty three patients received second line ChT after progression, 7 of them received it within the first year. Fifty four patients were followed up for 1 year. Two patients were lost after progression and couldn’t be reached for further treatment. A total of 320 cycles ChT were administered, 36 patients have completed 6 cycles. The overall response rate was 49% with 1 CR, 30 PR, 20 SD and 12 PD. Median follow up was 48 weeks, median time to progression 34 weeks, median survival time 48 weeks. One year survival was 51%. There was no Gr IV toxicity, 4 Gr Ill anemia (6.3%), 4 Gr Ill neutropenia (6.3%) 5 Gr Ill vomiting (7.9%). Conclusion: Cisplatin - Vinorelbine combination is an effective and well tolerated regimen in the treatment of advanced NSCLC patients. ElP 41
A Study of Gemcitabine and Carboplatin Nonsmall Cell Lung Cancer
P 42 El
NSCLC 2
SlOl
Cisplatin/Docetaxel(CDDP/TXT) as second-line treatment in advanced non-small cell lung cancer (NSCLC) patients pretreated with non-platinum-based regimens
Tiziana Prochilo’, Mara A. Cafferata”, Editta Baldinis, Andrea Ardizzoni4. ’ Div. of Medical Oncology/St. Chiara University Hospifal, Pisa, Italy; ‘Div. of Medical Oncology//ST; Geneva, Italy; 3 Dkof Medical Oncology/St. Chiara University Hospital, Piss, Italy; 4 Div of Medical OncologyNS7; Genova, ltaly
Purpose: In the present ongoing study we evaluate feasibility and activity of salvage CCDPFXT in advanced NSCLC patients (pts) receiving non-platinumcontaining regimens as first-line treatment. Patients and methods: Pts with stage IIIB/IV NSCLC, ECOG PS 5 2, progressive disease after non-platinum-based CT, were included. CDDP (75 mg/sqm day 1) and TXT (75 mg/sqm day 1) were both administered on a threeweek schedule for a maximum of 6 courses. Results: 16 pts were included; median age 64 years (47-73); PS 0 = 6, PS 1 = IO; stage lllB/IV = l/15; histology 8 squamous and 8 non-squamous. Most pts received Gemcitabine/lfosfamideA/inorelbine (GIN) as Ist-line treatment and 12/16 achieved a partial remission. Median interval from the end of first-line and the start of salvage therapy was 5 months (mos) (21 days-14 mos). A total of 55 courses were administered with a median of 3 courses (I-6) per pt. All pts were evaluable for toxicity: W.H.O. G 3/4 neutropenia was observed in 4 pts (one pt 25% reduction of TXT), but no episode of febrile neutropenia was reported. One pt experienced G3 anemia (25% reduction of both drugs); one pt reported G3 vomiting (25% reduction of both drugs); 4 pts experienced G3 fatigue (one pt 25% reduction of both drugs and one pt discontinued the treatment). G 2 neurotoxicity was observed in 4 pts after the fifth course of treatment. Other toxicities were mild. No toxic deaths were observed. Responses were assessed every 3 courses and 13 (81%) out of 16 pts were evaluable, 3 pts were not evaluable (1 early death, 1 stop for fatigue, 1 pt too early). No complete response was observed but 5 out of 13 pts achieved a partial remission for an overall response rate of 31% (95% Cl 13.8-68.4); 5 pts (31%) showed a disease stabilization and 3 pts progressed during treatment. The median overall survival was 7 months (i-31+). Conclusions: the combination of CDDP/TXT is feasible in this group of pts and its toxicity is acceptable. This douplet could be a proposed as 2nd-line treatment for good PS NSCLC pts who have been previously treated with nonplatinum-containing regimens.
in Advanced
Savitree Maoleekoonpairof ’ , Nopadol Soparattanapaisarn ‘, Sudsawad Laohavinifs, Kasarn Seetalarom ‘. 1 Pramongkufkloa Bangkok, Thai/and; 2 Rajavithee Hospital, Bangkok, Thailand
P 43 El Haspita/,
Objectives: To evaluate the activity of gemcitabine and carboplatin in patients with stage IIIB and IV NSCLC, in terms of response rate, time to progression and overall survival. Patients and methods: Eligible patients had histologically/ cytologically confirmed of NSCLC, stage IIIB or IV disease, performance status ECOG O-2, no age limit. Chemotherapy consisted of gemcitabine 1000 mg/m2 on dayl, 8 and carboplatin AUC 5 on day 8, every 28 days. A maximum of 6 cycles was administered. Clinical benefit was evaluated by using the Lung Cancer Symptoms Scale, consisted of performance status, appetite, coughing, hemoptysis, fatigue, dyspnea and pain. Results: A total of 42 patients were studied, median age 64 years, M:F 32:10, PS O-1/2 = 22/20 (53%/47%), stage IIB/IV = 11131 (26.2/73.8%), histology included adeno/squamous/bronchoalveolar/undifferentiated = 22/16/l/3. The total 165 cycles were administered and median number of cycles was 4 cycles. Non-hematologic toxicities were minimal including nausea and skin rash. Grade 3-4 toxicities included: anemia 12%, neutropenia 19%, and thrombocytopenia 7%, no major bleeding reported, two patients developed febrile neutropenia, no patients died of serious adverse events. The objective response was 21.4% (ICR, 8PR), time to progression = 4.6 months and median survival = 7.2 months. The median survival in patients with PS 1 and 2 were 8.3 and 5.4 months respectively. There waas no different in median survial in patients with stage IIIB and IV (7.3 and 7.8 mo. respectively). Clinical benefits were observed in over 50% of patients with PS2. Conclusion: The gemcitabine and carboplatin in 28-day cycle seems efficient and feasible. There were clinical benefits in patients with PS 2 which may not gain survival benefit.
Randomised Phase Ill Trial of DocetaxellCarboplatin vs. MICYMVP Chemotherapy in Inoperable Advanced Non-Small Cell Lung Cancer (NSCLC) - Do XPD Polymorphisms Predict for Sensitivity or Resistance to Platinum Based Chemotherapy
Richard Booton’, Daniel Campbells 1-1 Tim Ward’ L. Ashcroft3, Fiona Power3, Pat Taylor4, Paul Burt3, Gilbert Wierenga3, Nicholas Thatcher3. 7 Christie Hospital NHS Trust/Paterson institute for Cancer Research, Manchester, UK; 2 Paterson Institute for Cancer Research, Manchester, UK; 3 Christie Hospital NHS Trust, Manchester, UK; 4 Wythenshawe Hospital, Manchester, UK Platinum compounds are used extensively in the management of advanced NSCLC. However, approximately 50% of patients receiving a platinum based combination do not respond. Polymorphisms in DNA repair genes may influence the tumour response to platinum drugs. We have therefore examined XPD Lys751 Gln and Asp31 2Asn in 109 prospectively accrued patients participating in a randomised trial of docetaxel/carboplatin vs. MIC/MVP chemotherapy. Peripheral blood was used and stored at 4°C prior to DNA extraction using MasterPureTM DNA Purification Kit (Epicentre, Wisconsin, USA). Primers were designed to amplify the XPD polymorphisms using the Failsafe PCR System (Epicentre, Wisconsin, USA). Samples were sequenced using a sequencing primer and the ABI 7700 sequencer incorporating dye-terminator technology. Patient characteristics are: median age 64.5, females 32.7%, males 67.3%. Frequencies of XPD genotypes were Lys751Lys n=43, Lys751Gln n=47, Gln751Gln Stratification 751 Polymorphism Wild type (Wt) n=29 Heterozygote (Het) n=2s Homozygousvariantn=8 312 Polymorphism
Wild type (Wt) n=28 Heterozygote (Het) n=27 Homozygous variant n=9 Combined 312 & 751 Genotype Both alleles Wt n=23 Both alleles Het n=22 >2 variant alleles n=a Both alleles homo variant n=7
ORR (%)
SD (%)
PD (%)
NE (%)
31 28.6 25
27.6 28.6 25
27.6 25 50
13.7 17.6
25 33.3 22.2
26.6 26 33.3
25 29.6 44.4
21.4
30.4
30.4 31.8 25 28.6
26.1 27.3 50 57.1
13.0 9.1
31.8 25 14.3
11.1
P 40 L-J
Cisplatin and Vinorelbine chemotherapy for stage MB and IV non-small cell lung cancer: an experience from a Chest Diseases Hospital in Turkey
Nilgun Fatma Hatabay, Ferah Ece. SSK Sureyyapasa Chest and Cardiovascular Diseases Hospital, Istanbul-Turkey Istanbul, Turkey
Purpose: to evaluate the efficacy of cisplatin (CDDP) - vinorelbine (VNR) regimen in chemonaive (NSCLC).
patients with stage IlIE - IV nonsmall
cell lung cancer
Patients and Methods: From April 2000 to December 2001, 63 patients with advanced NSCLC were included in the study. Fifty nine patients were male and 4 female, median age was 57 years (37-76) ECOG performans status (PS) O/l was 40/23, stage IIIB/IV was 27/36. Histologic diagnosis was squamous cell lung cancer in 30 patients, adenocarcinoma in 22 and undifferentiated NSCLC in 11. Two patients had curative radiotherapy (RT) before chemotherapy (ChT). None of the patients had curative RT after ChT where as 15 had palliative RT for brain, bone metastases and pain relief. Treatment consisted of 30 mg/ms VNR on days I,8 and 70 mg/ms CDDP on day 1 of every 3 weeks. Results: All patients were evaluated for time to progression and overall response rate and toxicity. Twenty three patients received second line ChT after progression, 7 of them received it within the first year. Fifty four patients were followed up for 1 year. Two patients were lost after progression and couldn’t be reached for further treatment. A total of 320 cycles ChT were administered, 36 patients have completed 6 cycles. The overall response rate was 49% with 1 CR, 30 PR, 20 SD and 12 PD. Median follow up was 48 weeks, median time to progression 34 weeks, median survival time 48 weeks. One year survival was 51%. There was no Gr IV toxicity, 4 Gr Ill anemia (6.3%), 4 Gr Ill neutropenia (6.3%) 5 Gr Ill vomiting (7.9%). Conclusion: Cisplatin - Vinorelbine combination is an effective and well tolerated regimen in the treatment of advanced NSCLC patients. ElP 41
A Study of Gemcitabine and Carboplatin Nonsmall Cell Lung Cancer
P 42 El
NSCLC 2
SlOl
Cisplatin/Docetaxel(CDDP/TXT) as second-line treatment in advanced non-small cell lung cancer (NSCLC) patients pretreated with non-platinum-based regimens
Tiziana Prochilo’, Mara A. Cafferata”, Editta Baldinis, Andrea Ardizzoni4. ’ Div. of Medical Oncology/St. Chiara University Hospifal, Pisa, Italy; ‘Div. of Medical Oncology//ST; Geneva, Italy; 3 Dkof Medical Oncology/St. Chiara University Hospital, Piss, Italy; 4 Div of Medical OncologyNS7; Genova, ltaly
Purpose: In the present ongoing study we evaluate feasibility and activity of salvage CCDPFXT in advanced NSCLC patients (pts) receiving non-platinumcontaining regimens as first-line treatment. Patients and methods: Pts with stage IIIB/IV NSCLC, ECOG PS 5 2, progressive disease after non-platinum-based CT, were included. CDDP (75 mg/sqm day 1) and TXT (75 mg/sqm day 1) were both administered on a threeweek schedule for a maximum of 6 courses. Results: 16 pts were included; median age 64 years (47-73); PS 0 = 6, PS 1 = IO; stage lllB/IV = l/15; histology 8 squamous and 8 non-squamous. Most pts received Gemcitabine/lfosfamideA/inorelbine (GIN) as Ist-line treatment and 12/16 achieved a partial remission. Median interval from the end of first-line and the start of salvage therapy was 5 months (mos) (21 days-14 mos). A total of 55 courses were administered with a median of 3 courses (I-6) per pt. All pts were evaluable for toxicity: W.H.O. G 3/4 neutropenia was observed in 4 pts (one pt 25% reduction of TXT), but no episode of febrile neutropenia was reported. One pt experienced G3 anemia (25% reduction of both drugs); one pt reported G3 vomiting (25% reduction of both drugs); 4 pts experienced G3 fatigue (one pt 25% reduction of both drugs and one pt discontinued the treatment). G 2 neurotoxicity was observed in 4 pts after the fifth course of treatment. Other toxicities were mild. No toxic deaths were observed. Responses were assessed every 3 courses and 13 (81%) out of 16 pts were evaluable, 3 pts were not evaluable (1 early death, 1 stop for fatigue, 1 pt too early). No complete response was observed but 5 out of 13 pts achieved a partial remission for an overall response rate of 31% (95% Cl 13.8-68.4); 5 pts (31%) showed a disease stabilization and 3 pts progressed during treatment. The median overall survival was 7 months (i-31+). Conclusions: the combination of CDDP/TXT is feasible in this group of pts and its toxicity is acceptable. This douplet could be a proposed as 2nd-line treatment for good PS NSCLC pts who have been previously treated with nonplatinum-containing regimens.
in Advanced
Savitree Maoleekoonpairof ’ , Nopadol Soparattanapaisarn ‘, Sudsawad Laohavinifs, Kasarn Seetalarom ‘. 1 Pramongkufkloa Bangkok, Thai/and; 2 Rajavithee Hospital, Bangkok, Thailand
P 43 El Haspita/,
Objectives: To evaluate the activity of gemcitabine and carboplatin in patients with stage IIIB and IV NSCLC, in terms of response rate, time to progression and overall survival. Patients and methods: Eligible patients had histologically/ cytologically confirmed of NSCLC, stage IIIB or IV disease, performance status ECOG O-2, no age limit. Chemotherapy consisted of gemcitabine 1000 mg/m2 on dayl, 8 and carboplatin AUC 5 on day 8, every 28 days. A maximum of 6 cycles was administered. Clinical benefit was evaluated by using the Lung Cancer Symptoms Scale, consisted of performance status, appetite, coughing, hemoptysis, fatigue, dyspnea and pain. Results: A total of 42 patients were studied, median age 64 years, M:F 32:10, PS O-1/2 = 22/20 (53%/47%), stage IIB/IV = 11131 (26.2/73.8%), histology included adeno/squamous/bronchoalveolar/undifferentiated = 22/16/l/3. The total 165 cycles were administered and median number of cycles was 4 cycles. Non-hematologic toxicities were minimal including nausea and skin rash. Grade 3-4 toxicities included: anemia 12%, neutropenia 19%, and thrombocytopenia 7%, no major bleeding reported, two patients developed febrile neutropenia, no patients died of serious adverse events. The objective response was 21.4% (ICR, 8PR), time to progression = 4.6 months and median survival = 7.2 months. The median survival in patients with PS 1 and 2 were 8.3 and 5.4 months respectively. There waas no different in median survial in patients with stage IIIB and IV (7.3 and 7.8 mo. respectively). Clinical benefits were observed in over 50% of patients with PS2. Conclusion: The gemcitabine and carboplatin in 28-day cycle seems efficient and feasible. There were clinical benefits in patients with PS 2 which may not gain survival benefit.
Randomised Phase Ill Trial of DocetaxellCarboplatin vs. MICYMVP Chemotherapy in Inoperable Advanced Non-Small Cell Lung Cancer (NSCLC) - Do XPD Polymorphisms Predict for Sensitivity or Resistance to Platinum Based Chemotherapy
Richard Booton’, Daniel Campbells 1-1 Tim Ward’ L. Ashcroft3, Fiona Power3, Pat Taylor4, Paul Burt3, Gilbert Wierenga3, Nicholas Thatcher3. 7 Christie Hospital NHS Trust/Paterson institute for Cancer Research, Manchester, UK; 2 Paterson Institute for Cancer Research, Manchester, UK; 3 Christie Hospital NHS Trust, Manchester, UK; 4 Wythenshawe Hospital, Manchester, UK Platinum compounds are used extensively in the management of advanced NSCLC. However, approximately 50% of patients receiving a platinum based combination do not respond. Polymorphisms in DNA repair genes may influence the tumour response to platinum drugs. We have therefore examined XPD Lys751 Gln and Asp31 2Asn in 109 prospectively accrued patients participating in a randomised trial of docetaxel/carboplatin vs. MIC/MVP chemotherapy. Peripheral blood was used and stored at 4°C prior to DNA extraction using MasterPureTM DNA Purification Kit (Epicentre, Wisconsin, USA). Primers were designed to amplify the XPD polymorphisms using the Failsafe PCR System (Epicentre, Wisconsin, USA). Samples were sequenced using a sequencing primer and the ABI 7700 sequencer incorporating dye-terminator technology. Patient characteristics are: median age 64.5, females 32.7%, males 67.3%. Frequencies of XPD genotypes were Lys751Lys n=43, Lys751Gln n=47, Gln751Gln Stratification 751 Polymorphism Wild type (Wt) n=29 Heterozygote (Het) n=2s Homozygousvariantn=8 312 Polymorphism
Wild type (Wt) n=28 Heterozygote (Het) n=27 Homozygous variant n=9 Combined 312 & 751 Genotype Both alleles Wt n=23 Both alleles Het n=22 >2 variant alleles n=a Both alleles homo variant n=7
ORR (%)
SD (%)
PD (%)
NE (%)
31 28.6 25
27.6 28.6 25
27.6 25 50
13.7 17.6
25 33.3 22.2
26.6 26 33.3
25 29.6 44.4
21.4
30.4
30.4 31.8 25 28.6
26.1 27.3 50 57.1
13.0 9.1
31.8 25 14.3
11.1