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P-216 Clinical outcome for lymphoepithelioma-like carcinoma of the lung after chemoradiotherapy
S146
Poster Session 2/Chemotherapy:
cancer risk. These XPD variant alleles have been associated with the reduced repair of DNA adducts. Since 2000, 255 patients (p) of a planned 600 have been included in a three-arm randomized trial comparing surgery alone (SUR) versus three cycles of neoadjuvant paclitaxellcarboplatin (NEO) versus surgery followed by three cycles of the same regimen (ADJ). Signed genetic consent was obtained from all patients. XPD was analyzed from peripheral blood at baseline. Initial data is available for 148 p: 129 male, 19 female; 146 PS O-1; 75 squamous cell, 56 adenocarcinoma, 6 large cell, 11 unspecified; 20 stage IA, 81 IB, 6 IIA, 15 IIB, 21 IIIA (T3Nl); 66 XPD Lys751Lys 63 Lys751Gln 19 Gln751Gln 74 Asp312Asp, 59 Asp3lPAsn, 14 Asn312Asn. XPD genotypes are well-balanced across treatment arms, though the frequency of Lys751Gln is slightly higher in ADJ. 54 p were allocated to SUR, 52 to NEO, 42 to ADJ. Radiographic response with NEO: 3 (6%) complete response, 28 (60%) partial response, 14 (30%) stable disease. Lobectomy was performed in 63.5% of all p, pneumonectomy in 22%, bilobectomy in 6%, other procedures in remaining p. Actuarial disease-free and median survival (MS) have not been reached, but there is a trend towards lower survival with SUR (50% at 30 months [mlversus 90% with NE0 and 80% with ADJ). MS with SUR is 13.8 m for p with Lys751Gln and 23.4 m for p with Asp312Asn but has not been reached for p with other XPD genotypes. With NE0 and ADJ, MS has not been reached. These results indicate that p with XPD Lys751Gln and/or Asp312Asn have a high risk of relapse with surgery alone and can clearly benefit from either neoadjuvant or adjuvant chemotherapy. In contrast, chemotherapy benefit may be lower for p with other XPD genotypes, which have been linked to better DNA repair capacity. Complete comparison results will be presented.
I P 216
Clinical outcome for lymphoepithelioma-like the lung after chemoradiotherapy
carcinoma of
James C.M. Ho, W.K. Lam, B. Lam, Maria P. Wong, Kenneth W.T. Tsang. University of Hong Kong, Hong Kong, China
Background: Lymphoepithelioma-like
carcinoma (LELC) of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare form of nonsmall cell lung cancer. It predominantly affects young non-smoking Asians and is frequently believed to be resectable. However, there has only been limited experience with the use of palliative chemotherapy and radiotherapy in treating advanced LELC of the lung. Study objectives: To evaluate the tumor response, time to progression and survival of patients with advanced LELC of the lung who received chemoradiotherapy. Design and patients: We prospectively recruited cases of LELC of the lung with a standard clinical protocol. Patients with confirmed advanced LELC of the lung were given chemoradiotherapy treatment. Setting: A tertiary respiratory referral center. Results: There were 10 patients (5 males, age 47 f 9.8 years, median follow-up 22 months) with advanced LELC of the lung (1, 4, and 5 patients at TNM stage IIIA, 1118, and IV) who received systemic chemotherapy and radiotherapy. The primary chemotherapy regimen comprised of 5fluorouracil/leucovorin/cisplatin (FLP). The response rates to FLP were 60% partial response, 10% stable disease, and 30% progressive disease. Eight patients were given local radiotherapy. Five patients received salvage chemotherapy when disease progressed after primary chemotherapy. The overall median survival was 23.4 & 4.7 months. Conclusion: The encouraging response to combination chemotherapy (FLP) supports its use, along with radiotherapy, in unresectable LELC of the lung.
I- P 217
K ras mutations in serum DNA of early non-small-cell lung cancer (NSCLC) patients (p): A genetic analysis of an ongoing randomized neoadjuvantladjuvant paclitaxel/carboplatin trial
Jose Luis Manzano’ , ltziar De Aguirre ‘, Monica Botia’ , Jose Luis Ramirez’ , Bartomeu Massuti’, Cristina Queralt’ , Jose Miguel Sanchez’, Jose Almenarez3, Miguel Taron’, Rafael Rosell’. ’ Hospital Germans Trias i Pujol Sadalona, Spain; p Hospital Genera/ de Alicante, Alicante, Spain; 3 Hospital Universitario insular de Gran Canada, Gran Canaria, Spain K-ras mutations at codon 12, which are common in cancer and present in more than 30% of NSCLC, may be induced by carcinogen DNA adducts. We have identified serum DNA K-ras mutations in resected NSCLC p and examined their effect on survival. Since 2000, 255 p of a planned 600 have been included in a three-arm randomized trial comparing surgery alone (SUR) versus three cycles of neoadjuvant paclitaxel/carboplatin (NEO) versus surgery followed by three cycles of the same regimen (ADJ). Signed genetic consent was obtained from all p. K-ras was analyzed from peripheral blood at baseline. initial data is available for 86 p: 56 male, 8 female; 62 PS O-1; 32 squamous cell, 26 adenocarcinoma, 4 large cell, 2 unspecified; 9 stage IA, 32 IB, 6 IIA, 6 IIB, 17 IIIA (T3Ni). K-ras mutations were present in 6/23 p in SUR, 3117 p in NEO, and 6/24 p in ADJ. Radiographic response with NEO: 7 (44%) partial response, 7
NSCLC 2
(44%) stable disease. Lobectomy was performed in 58% of all p, pneumonectomy in 22%, bilobectomy in 9.4%, other procedures in remaining p. There was no significant association between K-ras status and tumor size, but the smallest median tumor size (2 cm) was observed in p with K-ras mutations in NEO. Actuarial disease-free and median survival have not been reached in any arm. There are no significant differences in survival according to K-ras status. However, disease-free survival with ADJ was 16 months for p without K-ras mutations and has not been reached for those with K-ras mutations; with NEO, p with K-ras mutations also showed a tendency towards better disease-free survival. Since this may be due to a lower DNA repair capacity conferred by K-ras mutations, further follow-up is required to clarify whether K-ras mutations in serum DNA could be a marker of chemosensitivity. Complete comparison results will be presented.
ElP 218
A phase II study of cisplatin and docetaxel administered as 3 consecutive weekly infusions for advanced NSCLC in elderly patients
Yuichiro Ohe’, Seiji Niho’, Koshiro Watanabe3, Akira Yokoyama4, Nagahiro Saijo’, Yutaka Nishiwakis. ’ National Cancer Center Hospital, Tokyo, Japan; *National Cancer Center Hospital East, Kashiwa, Japan; 3 Yokohama Municipal Citizen’s Hospital, Yokohama, Japan; 4 Niigata Cancer Center Hospita/, Niigata, Japan; 5 National Cancer Center Hosiptal East Kashiwa, Japan
Purpose: To evaluate the efficacy and safety of the treatment for advanced NSCLC in elderly patients aged 75 years or older we conducted a phase II study of cisplatin and docetaxel administered as 3 consecutive weekly infusions. Patients and Methods: Eligibility criteria included, chemotherapy-naive advanced non-small cell lung cancer, age 75 years or older, ECOG PS 0 or 1, measurable lesion, adequate organ functions and signed informed consent. Chemotherapy consisted of cisplatin 25 mg/m” and docetaxel 20 mg/m” on days 1, 8 and 15 every 4 weeks. Results: Between February 2000 and March 2002, 34 elderly patients with non-small cell lung cancer were entered and 33 (median: 77y, range: 75-88~) of them were treated in this study. The median number of treatment cycles was 3 (range I-15). There were 2 complete response and 15 partial response for an objective response rate of 52% (95%CI: 31-67%) in 33 treated patients. The median survival was 13.6 months; and the 1 -year and 2-year survival rates were 62% and 16%, respectively. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%) neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. Conclusion: Cisplatin and docetaxel administered as 3 consecutive weekly infusions was very effective and safe for elderly patients with chemotherapynaive NSCLC. The JCOG is conducting a phase Ill study of cisplatin and docetaxel versus docetaxel alone administered by 3 consecutive weekly infusions for elderly patients with NSCLC to examine the role of cisplatin for elderly patients I P 219
Preliminary Clinical and Pharmacokinetic Data for CT-2103 (XyotaxTM) in Patients with Non-Small Cell Lung Cancer (NSCLC)
Howard Burris’, Diana Shipley’, Anthony Greco’ , Suzanne Jones’, Noel Willicut’, Pamela Garzones, Mary G. Boltons. I The Sarah Cannon Cancer Center, Nashville, USA; ‘Cell Therapeutics, Inc., Seattle, USA CT-2103 (Xyotax’rM) is a high molecular weight drug polymer conjugate delivery system that is being developed in an attempt to make paclitaxel soluble in an aqueous solution (eliminates the need for CremophopEL), take advantage of tumor permeability and retention of paclitaxel, and minimize the toxicity of paclitaxel to normal organs. In animal studies, CT-21 03 had a higher maximum tolerated dose (MID) and increased antitumor efficacy when compared to paclitaxel in Cremophor@EL. This study was designed to determine the MTD, toxicity profile, and pharmacokinetics of CT-2103 in patients with previously treated (l2 prior regimens) NSCLC. To date, 8 patients (2F/8M; median age 63, range 49-77; median performance status 1; median number of prior regimens 2) have received a total of 24 cycles of treatment (range 1-5 cycles/patient) at dose levels of 235 mg/m* (3 patients) and 270 mg/m2 (5 patients) of conjugated paclitaxel. The drug is given as a 1 O-20 minute intravenous infusion every 3 weeks. The major toxicity encountered to date has been neutropenia (Gr 3 = 4, Gr 4 = I), with 1 patient experiencing Gr 2 neuropathy at the highest dose level. No other Gr 3/4 drug-related toxicities have been reported. One partial response has been reported in a patient previously treated with gemcitabine/vinorelbine and IRESSA. Pharmacokinetic data obtained in Cycles 1 and 3 indicate that CT-2103 has a long elimination phase (T 1,s >I30 hours) and that distribution is limited to plasma volume (mean clearance x 200 ml/hr; mean V,, 4.0f2.5L). There was no evidence for drug accumulation. The AUC of unconjugated paclitaxel was ~6% of the AUC of CT-2103. Patient accrual currently continues at the 270 mg/m” dose level and the MTD remains to be determined.
Poster Session 2/Chemotherapy:
cancer risk. These XPD variant alleles have been associated with the reduced repair of DNA adducts. Since 2000, 255 patients (p) of a planned 600 have been included in a three-arm randomized trial comparing surgery alone (SUR) versus three cycles of neoadjuvant paclitaxellcarboplatin (NEO) versus surgery followed by three cycles of the same regimen (ADJ). Signed genetic consent was obtained from all patients. XPD was analyzed from peripheral blood at baseline. Initial data is available for 148 p: 129 male, 19 female; 146 PS O-1; 75 squamous cell, 56 adenocarcinoma, 6 large cell, 11 unspecified; 20 stage IA, 81 IB, 6 IIA, 15 IIB, 21 IIIA (T3Nl); 66 XPD Lys751Lys 63 Lys751Gln 19 Gln751Gln 74 Asp312Asp, 59 Asp3lPAsn, 14 Asn312Asn. XPD genotypes are well-balanced across treatment arms, though the frequency of Lys751Gln is slightly higher in ADJ. 54 p were allocated to SUR, 52 to NEO, 42 to ADJ. Radiographic response with NEO: 3 (6%) complete response, 28 (60%) partial response, 14 (30%) stable disease. Lobectomy was performed in 63.5% of all p, pneumonectomy in 22%, bilobectomy in 6%, other procedures in remaining p. Actuarial disease-free and median survival (MS) have not been reached, but there is a trend towards lower survival with SUR (50% at 30 months [mlversus 90% with NE0 and 80% with ADJ). MS with SUR is 13.8 m for p with Lys751Gln and 23.4 m for p with Asp312Asn but has not been reached for p with other XPD genotypes. With NE0 and ADJ, MS has not been reached. These results indicate that p with XPD Lys751Gln and/or Asp312Asn have a high risk of relapse with surgery alone and can clearly benefit from either neoadjuvant or adjuvant chemotherapy. In contrast, chemotherapy benefit may be lower for p with other XPD genotypes, which have been linked to better DNA repair capacity. Complete comparison results will be presented.
I P 216
Clinical outcome for lymphoepithelioma-like the lung after chemoradiotherapy
carcinoma of
James C.M. Ho, W.K. Lam, B. Lam, Maria P. Wong, Kenneth W.T. Tsang. University of Hong Kong, Hong Kong, China
Background: Lymphoepithelioma-like
carcinoma (LELC) of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare form of nonsmall cell lung cancer. It predominantly affects young non-smoking Asians and is frequently believed to be resectable. However, there has only been limited experience with the use of palliative chemotherapy and radiotherapy in treating advanced LELC of the lung. Study objectives: To evaluate the tumor response, time to progression and survival of patients with advanced LELC of the lung who received chemoradiotherapy. Design and patients: We prospectively recruited cases of LELC of the lung with a standard clinical protocol. Patients with confirmed advanced LELC of the lung were given chemoradiotherapy treatment. Setting: A tertiary respiratory referral center. Results: There were 10 patients (5 males, age 47 f 9.8 years, median follow-up 22 months) with advanced LELC of the lung (1, 4, and 5 patients at TNM stage IIIA, 1118, and IV) who received systemic chemotherapy and radiotherapy. The primary chemotherapy regimen comprised of 5fluorouracil/leucovorin/cisplatin (FLP). The response rates to FLP were 60% partial response, 10% stable disease, and 30% progressive disease. Eight patients were given local radiotherapy. Five patients received salvage chemotherapy when disease progressed after primary chemotherapy. The overall median survival was 23.4 & 4.7 months. Conclusion: The encouraging response to combination chemotherapy (FLP) supports its use, along with radiotherapy, in unresectable LELC of the lung.
I- P 217
K ras mutations in serum DNA of early non-small-cell lung cancer (NSCLC) patients (p): A genetic analysis of an ongoing randomized neoadjuvantladjuvant paclitaxel/carboplatin trial
Jose Luis Manzano’ , ltziar De Aguirre ‘, Monica Botia’ , Jose Luis Ramirez’ , Bartomeu Massuti’, Cristina Queralt’ , Jose Miguel Sanchez’, Jose Almenarez3, Miguel Taron’, Rafael Rosell’. ’ Hospital Germans Trias i Pujol Sadalona, Spain; p Hospital Genera/ de Alicante, Alicante, Spain; 3 Hospital Universitario insular de Gran Canada, Gran Canaria, Spain K-ras mutations at codon 12, which are common in cancer and present in more than 30% of NSCLC, may be induced by carcinogen DNA adducts. We have identified serum DNA K-ras mutations in resected NSCLC p and examined their effect on survival. Since 2000, 255 p of a planned 600 have been included in a three-arm randomized trial comparing surgery alone (SUR) versus three cycles of neoadjuvant paclitaxel/carboplatin (NEO) versus surgery followed by three cycles of the same regimen (ADJ). Signed genetic consent was obtained from all p. K-ras was analyzed from peripheral blood at baseline. initial data is available for 86 p: 56 male, 8 female; 62 PS O-1; 32 squamous cell, 26 adenocarcinoma, 4 large cell, 2 unspecified; 9 stage IA, 32 IB, 6 IIA, 6 IIB, 17 IIIA (T3Ni). K-ras mutations were present in 6/23 p in SUR, 3117 p in NEO, and 6/24 p in ADJ. Radiographic response with NEO: 7 (44%) partial response, 7
NSCLC 2
(44%) stable disease. Lobectomy was performed in 58% of all p, pneumonectomy in 22%, bilobectomy in 9.4%, other procedures in remaining p. There was no significant association between K-ras status and tumor size, but the smallest median tumor size (2 cm) was observed in p with K-ras mutations in NEO. Actuarial disease-free and median survival have not been reached in any arm. There are no significant differences in survival according to K-ras status. However, disease-free survival with ADJ was 16 months for p without K-ras mutations and has not been reached for those with K-ras mutations; with NEO, p with K-ras mutations also showed a tendency towards better disease-free survival. Since this may be due to a lower DNA repair capacity conferred by K-ras mutations, further follow-up is required to clarify whether K-ras mutations in serum DNA could be a marker of chemosensitivity. Complete comparison results will be presented.
ElP 218
A phase II study of cisplatin and docetaxel administered as 3 consecutive weekly infusions for advanced NSCLC in elderly patients
Yuichiro Ohe’, Seiji Niho’, Koshiro Watanabe3, Akira Yokoyama4, Nagahiro Saijo’, Yutaka Nishiwakis. ’ National Cancer Center Hospital, Tokyo, Japan; *National Cancer Center Hospital East, Kashiwa, Japan; 3 Yokohama Municipal Citizen’s Hospital, Yokohama, Japan; 4 Niigata Cancer Center Hospita/, Niigata, Japan; 5 National Cancer Center Hosiptal East Kashiwa, Japan
Purpose: To evaluate the efficacy and safety of the treatment for advanced NSCLC in elderly patients aged 75 years or older we conducted a phase II study of cisplatin and docetaxel administered as 3 consecutive weekly infusions. Patients and Methods: Eligibility criteria included, chemotherapy-naive advanced non-small cell lung cancer, age 75 years or older, ECOG PS 0 or 1, measurable lesion, adequate organ functions and signed informed consent. Chemotherapy consisted of cisplatin 25 mg/m” and docetaxel 20 mg/m” on days 1, 8 and 15 every 4 weeks. Results: Between February 2000 and March 2002, 34 elderly patients with non-small cell lung cancer were entered and 33 (median: 77y, range: 75-88~) of them were treated in this study. The median number of treatment cycles was 3 (range I-15). There were 2 complete response and 15 partial response for an objective response rate of 52% (95%CI: 31-67%) in 33 treated patients. The median survival was 13.6 months; and the 1 -year and 2-year survival rates were 62% and 16%, respectively. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%) neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. Conclusion: Cisplatin and docetaxel administered as 3 consecutive weekly infusions was very effective and safe for elderly patients with chemotherapynaive NSCLC. The JCOG is conducting a phase Ill study of cisplatin and docetaxel versus docetaxel alone administered by 3 consecutive weekly infusions for elderly patients with NSCLC to examine the role of cisplatin for elderly patients I P 219
Preliminary Clinical and Pharmacokinetic Data for CT-2103 (XyotaxTM) in Patients with Non-Small Cell Lung Cancer (NSCLC)
Howard Burris’, Diana Shipley’, Anthony Greco’ , Suzanne Jones’, Noel Willicut’, Pamela Garzones, Mary G. Boltons. I The Sarah Cannon Cancer Center, Nashville, USA; ‘Cell Therapeutics, Inc., Seattle, USA CT-2103 (Xyotax’rM) is a high molecular weight drug polymer conjugate delivery system that is being developed in an attempt to make paclitaxel soluble in an aqueous solution (eliminates the need for CremophopEL), take advantage of tumor permeability and retention of paclitaxel, and minimize the toxicity of paclitaxel to normal organs. In animal studies, CT-21 03 had a higher maximum tolerated dose (MID) and increased antitumor efficacy when compared to paclitaxel in Cremophor@EL. This study was designed to determine the MTD, toxicity profile, and pharmacokinetics of CT-2103 in patients with previously treated (l2 prior regimens) NSCLC. To date, 8 patients (2F/8M; median age 63, range 49-77; median performance status 1; median number of prior regimens 2) have received a total of 24 cycles of treatment (range 1-5 cycles/patient) at dose levels of 235 mg/m* (3 patients) and 270 mg/m2 (5 patients) of conjugated paclitaxel. The drug is given as a 1 O-20 minute intravenous infusion every 3 weeks. The major toxicity encountered to date has been neutropenia (Gr 3 = 4, Gr 4 = I), with 1 patient experiencing Gr 2 neuropathy at the highest dose level. No other Gr 3/4 drug-related toxicities have been reported. One partial response has been reported in a patient previously treated with gemcitabine/vinorelbine and IRESSA. Pharmacokinetic data obtained in Cycles 1 and 3 indicate that CT-2103 has a long elimination phase (T 1,s >I30 hours) and that distribution is limited to plasma volume (mean clearance x 200 ml/hr; mean V,, 4.0f2.5L). There was no evidence for drug accumulation. The AUC of unconjugated paclitaxel was ~6% of the AUC of CT-2103. Patient accrual currently continues at the 270 mg/m” dose level and the MTD remains to be determined.