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Phase II trial of i.v. navelbine (NVB) and cisplatin (CDDP) in inoperable locally advanced or disseminated NSCLC
s34
Abstracts
characteristics of pts are well balanced in the two arms. Overall median age (range): 74 years (70-86); male gender: 87%; stage IV: 73%; PS (O/1/2): 18%/58%/24%. In the VNR arm a 20% response rate (95% CI: 12-32) was found. Toxicity was rare: G4 neutropenia, G3-4 constipation and G3 alopecia (4% of pts each); G4 leukopenia, G3 anemia and G3 vomiting (1% of pts each). QoL analysis will be ready for the meeting. Conclusion: Single agent VNR improves survival of advanced NSCLC elderly pts, without significant toxicity. The magnitude of the effect on survival is similar to that reported with cisplatinum-based polychemotherapy in advanced NSCLC adult pts. Phase II trial of i.v. navelhine (NVB) and cisplatin (CDDP) inoperable locally advanced or disseminated NSCLC
in
Goedhals’ L, Bezwoda’ W, Vorobiof’ D, Van Der Merwe’ A, Jordaan’ JP, Barnardt’ P, Bassompierre P, Lategan A, BurilIon J-P, Danel’ P. ‘South Afn’ca, 21nstitut de Recherche Pierre
this schedule. Chemotherapy consisted of VRL 8 mg/m* iv. bolus on day 1, immediately followed by a 4-day CI, through a central venous catheter, repeated every 21 days. The 4-day CI dose of VRL was escalated as follows: dose level (DL) 1 = 8 mg/m*/day X 4 days (32); DL2 = 9 mg/m*/day X 4 days (36); DL3 = 10 mg/m*/day X 4 days (40); DL4 = 11 mg/m*/day X 4 days (44); DL5 = 12 mg/m*/day X 4 day (48). A new DL was started when dose limiting toxicity (DLT) did not appear in 2 2/3 patients (pts). Chemotherapy in each DL was administered until DLT or disease progression. Dose was modified on appearance of DLT, decreasing by two full DL for the next cycles. Since June 1996, 23 chemo-naive pts have been enrolled: stage III-B one pt, stage IV 22 pts; sex M/F 20/3; median PS 1 (O-2); median age 55 years (33-67). At present, 113 cycles have been administered with a median of 3 (l-12) cycles per pt. Toxicity:
Fabre.
New drugs with promising activity have been identified for NSCLC treatment, and NVB has already been shown to increase the survival rate in randomised trials. Large European and American multicentre studies have shown that the results of NVB + CDDP combination had a statistically superior survival, compared with standard therapy [Le Chevalier/JCO 19941. Based on these results, this study has been conducted in South Africa in order to test this combination in our patients (pts): NVB 30 mg/m* Dl and D8 + CDDP 100 mg/m’ Dl, every 21 days, for six cycles max. Thirty-five previously untreated pts were included from 09/95 to 12/96. Thirty pts are evaluable for response, 32 for tolerance, with the following characteristics: median age 55.8 years (42-68), PS/O-1 = 77%, 2 = 23%; 56% squam. cell carcinoma, 28% adenoca, 16% large cell carcinoma. Stage IIIA = 17.2%, IIIB = 20.7%, IV = 62.1%. One hundred and sixteen courses were administered in total. The overall response rate was 41.5%: 1 CR/ 9 PR (95 Cl 21.8-61.2%), one further patient obtained an objective response but was not available for confirmation. WHO G3/4 neutropenia in nine pts with only three G3 infection; 19% of cycles with WHO G3 nausea/vomiting, WHO G2-3 constipation in 8.7% of cycles (two pts G3). Two pts presented G2 peripheral neuropathy. WHO G2/3 alopecia in 22% of pts, two episodes of G3 local phlebitis. Other side effects were uncommon. These preliminary results confirm that the combination of NVB + CDDP have major antitumour activity in NSCLC with a manageable tolerance. Continuous infusion vinorelbine small cell lung cancer (NSCLC).
(VRL) for A phase I/II
advanced study
Oncology
Section,
Hospital
Carlos
Haya,
#pts #cycles DLT per DL per DL
1 2
8/32 8/36
3 4
17 28
3
8/40
5
30
4
8/44
5
24
5
8/48
6
14
DLT # pts
Febrile neutropenia Neutropenia G4 and mucositis G3 Febrile neutropenia Febrile neutropenia and mucositis G3
O/3 l/4 l/5 l/5 3/6
Other toxicities were manageable: alopecia G2 in eight pts (35%), mucositis G2 five pts (22%0), constipation G2 four pts (17%), diarrhoea G2 three pts (13%), mild astenia four pts (17%), and mild dyspnea two pts (9%). Activity: 18 of 23 pts are evaluable for response (five too early), PR three pts (17%), MR one pt (6%), NC five pts (27%), and PD nine pts (50%) were observed. Conclusions: (1) DLTs were neutropenia and mucositis. (2) MTD in this setting is 8 mg/m’ (bolus) on day 1, followed by 11 mg/m*/day (CI) X 4 days. (3) Preliminary results indicate encouraging activity and low toxicity.
non-
Carabantes F, Benavides M, Cobo M, Hebrero ML, Trujillo R, G6mez D, de la Ggndara I, Bret6n JJ, Paredes G, JuLrez C. Medical Spain.
DL BoIus/4-day CI (mg/m*)
Mn’laga,
To increase the therapeutic index of VRL in NSCLC, a phase I/II trial of this agent administered by continuous infusion (Cl) was conducted to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and activity of
Prolonged oral etoposide in combination with cisplatin (oral EP) for non-small cell lung cancer
intravenous (NSCLC)
Park K, Kim K, Jeong HS, Lee JT, Kim WS, Yoon SS, Kang WK, Lee HG, Kim H, Rhee CH, Park CH. Dept. OfMedicine, Samsung Medicine,
Medical Center, Seoul, Korea
Sungkyunkwan
University,
College
of
Etoposide is a schedule-dependent agent and has a synergistic activity with cisplatin. We conducted prolonged oral etoposide with cisplatin for previously untreated NSCLC pts.
Abstracts
characteristics of pts are well balanced in the two arms. Overall median age (range): 74 years (70-86); male gender: 87%; stage IV: 73%; PS (O/1/2): 18%/58%/24%. In the VNR arm a 20% response rate (95% CI: 12-32) was found. Toxicity was rare: G4 neutropenia, G3-4 constipation and G3 alopecia (4% of pts each); G4 leukopenia, G3 anemia and G3 vomiting (1% of pts each). QoL analysis will be ready for the meeting. Conclusion: Single agent VNR improves survival of advanced NSCLC elderly pts, without significant toxicity. The magnitude of the effect on survival is similar to that reported with cisplatinum-based polychemotherapy in advanced NSCLC adult pts. Phase II trial of i.v. navelhine (NVB) and cisplatin (CDDP) inoperable locally advanced or disseminated NSCLC
in
Goedhals’ L, Bezwoda’ W, Vorobiof’ D, Van Der Merwe’ A, Jordaan’ JP, Barnardt’ P, Bassompierre P, Lategan A, BurilIon J-P, Danel’ P. ‘South Afn’ca, 21nstitut de Recherche Pierre
this schedule. Chemotherapy consisted of VRL 8 mg/m* iv. bolus on day 1, immediately followed by a 4-day CI, through a central venous catheter, repeated every 21 days. The 4-day CI dose of VRL was escalated as follows: dose level (DL) 1 = 8 mg/m*/day X 4 days (32); DL2 = 9 mg/m*/day X 4 days (36); DL3 = 10 mg/m*/day X 4 days (40); DL4 = 11 mg/m*/day X 4 days (44); DL5 = 12 mg/m*/day X 4 day (48). A new DL was started when dose limiting toxicity (DLT) did not appear in 2 2/3 patients (pts). Chemotherapy in each DL was administered until DLT or disease progression. Dose was modified on appearance of DLT, decreasing by two full DL for the next cycles. Since June 1996, 23 chemo-naive pts have been enrolled: stage III-B one pt, stage IV 22 pts; sex M/F 20/3; median PS 1 (O-2); median age 55 years (33-67). At present, 113 cycles have been administered with a median of 3 (l-12) cycles per pt. Toxicity:
Fabre.
New drugs with promising activity have been identified for NSCLC treatment, and NVB has already been shown to increase the survival rate in randomised trials. Large European and American multicentre studies have shown that the results of NVB + CDDP combination had a statistically superior survival, compared with standard therapy [Le Chevalier/JCO 19941. Based on these results, this study has been conducted in South Africa in order to test this combination in our patients (pts): NVB 30 mg/m* Dl and D8 + CDDP 100 mg/m’ Dl, every 21 days, for six cycles max. Thirty-five previously untreated pts were included from 09/95 to 12/96. Thirty pts are evaluable for response, 32 for tolerance, with the following characteristics: median age 55.8 years (42-68), PS/O-1 = 77%, 2 = 23%; 56% squam. cell carcinoma, 28% adenoca, 16% large cell carcinoma. Stage IIIA = 17.2%, IIIB = 20.7%, IV = 62.1%. One hundred and sixteen courses were administered in total. The overall response rate was 41.5%: 1 CR/ 9 PR (95 Cl 21.8-61.2%), one further patient obtained an objective response but was not available for confirmation. WHO G3/4 neutropenia in nine pts with only three G3 infection; 19% of cycles with WHO G3 nausea/vomiting, WHO G2-3 constipation in 8.7% of cycles (two pts G3). Two pts presented G2 peripheral neuropathy. WHO G2/3 alopecia in 22% of pts, two episodes of G3 local phlebitis. Other side effects were uncommon. These preliminary results confirm that the combination of NVB + CDDP have major antitumour activity in NSCLC with a manageable tolerance. Continuous infusion vinorelbine small cell lung cancer (NSCLC).
(VRL) for A phase I/II
advanced study
Oncology
Section,
Hospital
Carlos
Haya,
#pts #cycles DLT per DL per DL
1 2
8/32 8/36
3 4
17 28
3
8/40
5
30
4
8/44
5
24
5
8/48
6
14
DLT # pts
Febrile neutropenia Neutropenia G4 and mucositis G3 Febrile neutropenia Febrile neutropenia and mucositis G3
O/3 l/4 l/5 l/5 3/6
Other toxicities were manageable: alopecia G2 in eight pts (35%), mucositis G2 five pts (22%0), constipation G2 four pts (17%), diarrhoea G2 three pts (13%), mild astenia four pts (17%), and mild dyspnea two pts (9%). Activity: 18 of 23 pts are evaluable for response (five too early), PR three pts (17%), MR one pt (6%), NC five pts (27%), and PD nine pts (50%) were observed. Conclusions: (1) DLTs were neutropenia and mucositis. (2) MTD in this setting is 8 mg/m’ (bolus) on day 1, followed by 11 mg/m*/day (CI) X 4 days. (3) Preliminary results indicate encouraging activity and low toxicity.
non-
Carabantes F, Benavides M, Cobo M, Hebrero ML, Trujillo R, G6mez D, de la Ggndara I, Bret6n JJ, Paredes G, JuLrez C. Medical Spain.
DL BoIus/4-day CI (mg/m*)
Mn’laga,
To increase the therapeutic index of VRL in NSCLC, a phase I/II trial of this agent administered by continuous infusion (Cl) was conducted to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and activity of
Prolonged oral etoposide in combination with cisplatin (oral EP) for non-small cell lung cancer
intravenous (NSCLC)
Park K, Kim K, Jeong HS, Lee JT, Kim WS, Yoon SS, Kang WK, Lee HG, Kim H, Rhee CH, Park CH. Dept. OfMedicine, Samsung Medicine,
Medical Center, Seoul, Korea
Sungkyunkwan
University,
College
of
Etoposide is a schedule-dependent agent and has a synergistic activity with cisplatin. We conducted prolonged oral etoposide with cisplatin for previously untreated NSCLC pts.