- Email: [email protected]
Phase II study of paclitaxel, ifosfamide and carboplatin with filgrastim support in advanced non-small cell lung cancer (NSCLC)
Chemotherapy/Paclitaxel three cycles and 6/10 completed all 6 cycles of therapy. 9 pts in this group were evaluable for response and there were 2PR/1CR. Survival for pts with PS = 2 was 6.4 months. Pts age > 70 also had acceptable toxicity with grade 3/4 neutropenia: 2, Pits: 2, infection: 1 for the C/G portion, and grade 3/4 neutropenia: 2 on the paclitaxel portion. 7/9 pts completed the first three cycles and 5/9 completed all six cycles. There was 1CR/1PR. Median survival was 13.6 months. Conclusions: The sequential regimen of carboplatin/gemcitabine followed by paclitaxel has acceptable toxicity and promising response and survival in patients with PS = 2 or age > 70 years, The result for PS = 2 pts is comparable, if not superior to, the recent results of several regimens reported by ECOG in terms of response and survival. Though the overall rate of grade 3/4 toxicity was similar to the ECOG, these were mostly laboratory abnormalities and the majority of pts recovered sufficiently to receive further treatment. However, the numbers are small. Further evaluation of this regimen in these populations is warranted. Supported by Eli Lilly Oncology
~-0~ls cisplatin necessary for the treatment of non-small cell lung cancer (NSCLC)? - Analysis of consecutive trials of paclitaxel in NSCLC K. Kubota 1, ¥. Nishiwaki 1, A. Yokoyama2, S. Yoneda3, T. Tamura4, K. Watanabe 5, N. Saijo4. 1National Cancer Center Hospital East; 2Niigata Cancer Center Hospital; 3Saitama Cancer Center; 4National Cancer Center Hospital; 5 Yokohama Municipal Citizen's Hospital, Japan Paclitaxel (P) has unique mechanisms of action and is active in NSCLC. Because benefit of combination chemotherapy of P with other agents has not been demonstrated, we conducted an analysis of consecutive trials of P, which included phase II study of P alone and P/cisplatin. In P alone study, 210 mg/m 2 of P was administered as 3-hour infusion and repeated at 21-day interval. Eighty mg/m 2 of cisplatin and 180 mg/m 2 of P (3-hour infusion) were repeated at 21day interval in P/cisplatin study. Eligibility criteria are similar between two studies except for PS (0-2 in P alone, 0-1 in P/cisplatin) and stage (inoperable IIIA/IIIB and IV in P alone, IIIB and IV in P/cisplatin). Baseline demographics of the total 92 patients (pts), response and toxicities are summarized.
No. of pts Median age (range) Male (%) PS 0/1/2 Adeno/Squamous/others IIINIIIB/IV Response rate (%) Neutropenia Grade 3 + 4 (%) Nausea and vomiting (%) Peripheral neuropathy (%)
Paclitaxel alone
Paclitaxel/cisplatin
60 63 (27-74) 45 (75) 14/38/8 41/14/5 5/6/49 38 82 28 70
32 61 (43-:,71) 22 (69) 9/23/27/4/1 -/5/27 31 53 78 47
Survival data will be presented at the meeting. There was no difference in response rate between the two studies. Adding of cisplatin failed to show an advantage over P alone. In conclusion, randomized trials of paclitaxel with or without cisplatin are warranted.
[•
17
Paclitaxel and cisplatin in stage IV non-small cell lung cancer: A GETICS phase II study
A.V. Jaremtchuk, E,E Aman, J.J. Zarba, M Salvadori, R. Alvarez, F. Marmissolle. GETICS, Comodoro Rivadavia; GETICS, Buenos Aires; GETICS, Yerba Buena; GETICS, Santa Rosa; GETICS (Grupo de Estudio Tratamiento e InvestigaciOn del C.ncar del Sur), Argentina
Background: Stage is one of the most important prognostic factors in NSCLC. Unfortunately several studies evaluate chemotherapy regimens in advanced disease pooled stage III and IV patients. Purpose: To evaluate the efficacy, toxicity and survival rate of stage IV NSCLC patients treated with paclitaxel-cisplatin combination. Patients and Methods: Chemotherapy-naive patients with histologically confirmed satge IV NSCLC, ECOG PS 0-1, adequate bone marrow and organ function and measurable disease were eligible for the study. Paclitaxel was administered at a dose of 175 rag/m2, threehour e.v. infusion on day 1 followed by Cisplatin at a dose of 100 rag/m2 with appropriate hydration on day 2. Treatment was repeated every 3 weeks. Results: Thirty-two patients were enrolled, median age was 54 years (range 36 to 74 years). Seventy-five percent of patients were males, 50% had edenocarcinoma and 31% had >10% weight loss. Ninety-one courses were administered and 28 patients received at least two courses of PC regimen. One patient achieved a complete response and 7 patients achieved a partial response for an overall response rate of 25%. The median time to progression, median survival time and one year survival rate were 25 weeks, 41 weeks and 28% respectively. Grade 3/4 leucopenia, thrombocytopenia and anemia were observed in 21%, 6% and 6%. Neuretoxicity grade 2 were observed in 12.5% of patients. No toxic deaths were reported. Conclusion: The data show that paclitaxel plus cisplatin is a welltolerated and active regimen in stage IV NSCLC patients,
15-• Phase II study of paclitaxel, ifosfamide and carboplaUn with fllgrastim support in advanced non-small cell lung cancer (NSCLC)
A.M. Mauer, R.H. Ansari, P.C. Hoffman, T.G. Gabrys. University of Chicago Phase II Network, Chicago, IL, USA Based on the activity observed with the doublet combinations of paclitaxel/carboplatin and paclitaxel/ifosfamide (Annals Oncol 1996, 7: 314-6) in NSCLC, we undertook a phase II study of the triplet combination of paclitaxel, ifosfamide, and carboplatin in patients with advanced NSCLC. Doses and schedule of therapy were based upon phase I study of the triplet regimen completed at our institution. The regimen included paclitaxel (200 mg/m2 per 1 hour on day 1), carboplatin (AUC = 5 on day 2), and ifosfamicle (1500 mg/m2 on days 1 & 2) with Mesna (300 mg/m2 on days 1 & 2) with prophylactic filgrastim support starting on day 4 until ANC > 10,000. Eligibility criteria included stage IIIB (pleural efffusion)/IV NSCLC, measurable disease, normal bone marrow, hepatic, renal function. Patients were allowed to have to have one prior therapy with an investigational agent. Asymptomatic brain metastases were allowed. Fifty patients received protocol therapy. Pt characteristics: male-32; female-18; median age 62; median CALGB performance status-I; stage IIIB-8/IV-42; prior single agent experimental chemotherapy-I; prior chest radiotherapy-2. Median number of cycles administered was 4. Grade 4 hematologic toxicity included thrombocytopenia (6 pts) and neutropenia (7 pts) with neutropenic fever in 1 patient. Non-hematologic toxicity grade > 3 included: vomiting (3 pts), reversible azotemia (grade 3-1 pt), peripheral neuropathy (5 pts) and neurocortical (2 pts). Out of the 42 patients assessed for response, 10 partial responses were noted for an overall response rate of 24%. At a median follow up time of 11.3 months, the median survival is 13.4 months. This large phase II study confirms the feasibility and activity of this triplet regimen in patients with advanced non-small cell lung cancer.
18
Chemotherapy/Mesotheliome
Wednesday, 13 September 2000
10:30-12:00
ORAL SESSION
Chemotherapy/Mesotheliome
•
Combined treatment of malignant mssothelioma (MM) of the pleura with high dose Methotrexate (Mtx), and interferons alfa (IFA) and gamma (IFG)
O. Brodin, A. Knuuttila, M. Halme, H. Strander, C.J. LindEn, G. Hillerdal, K. Mattsson. Oncology, South Hospital, Stockholm;
Radiumhemmet, Karolinska Hospital, Stockholm; Medicine, University Hospital, Lund; Lung Medicine, University Hospital, Uppsala, Sweden, Medicine, University Central Hospital, Helsinki, Finland Median survival of patients with MM has been reported to be only 9-12 months. A response-rate of 37% has been reported for high dose Mtx. Also treatments with sc IFA and intraperitoneally IFG have accomplished responses (12% and 24%, respectivelly). We hoped to improve treatment result further by combining all three drugs. Patients with verified MM stage II-IV were included in this mutticentric phase II study. Marker lesions were identified on CT-scan taken before start of treatment and followed during and after treatment. Treatment consisted of Mtx given at a total dose of 3000 mg in each patient, together with Leucovorin rescue for totally 6 courses. IFA was given sc 3 milj IE for 8 days between each course and IFG 40 mikrog at 3 occasions between each course. After cessation of MTX, the IFA and IFG treatments proceeded at lower dosage. Forty-six patients were included. Responses, all partial, were found in 12 patients (27%). Toxicity was mainly haematological. No lethal toxicity was registered. Preliminarily, median survival is 13 months. The respons rate with these three drugs was worse than that reported with solely Mtx. If this was due to differences in response evaluation, if the 3 drugs interacted subtractively or if random factors have influenced the result, is an open question. Besides, this combined treatment was complicated and expensive and there is no indication that it improved median survival.
~ - ] Phase II trial of vinorelbine and oxaliplatin in patients with malignant pleural mesothelioma J.P.C. Steele, J. Shamash, M.T. Evans, N.H. Gower, RM. Rudd. St Bartholomew's Hospital, London, UK Introduction: The increasing incidence of malignant pleural mesothelioma (MPM) in Europe has led to renewed effort in the search for effective treatments for this poor-prognosis disease. We recently reported encouraging response rates in a phase II trial with single-agent vinorelbine (Proc ASCO 1999: 18: 490). This data prompted further examination of this semi-synthetic vinca alkaloid in combination with the new-generation platinum agent oxaliplatin. The apparent synergy between vinorelbine and platinum agents makes this a logical next step. Treatment Plan: We are examining the efficacy of the combination of vinorelbine (Navelbine, Pierre Fabra, France) and oxaliplatin (EIoxat/n, Sanofi, France) in an open phase II study in patients (pts) with previously untreated MPM. Entry criteria include: ECOG performance status of 0-2; measurable or evaluable disease; adequate hepatic, renal and haematologic reserve for platinum-based treatment. Pts with medical conditions that preclude the use of chemotherapy; active infection; brain metastases; or a history of prior malignancy are excluded. Treatment involves the intravenous administration of vinorelbine 30 rag/m2 on days 1 and 8 of a 21-day cycle and oxaliplatin 130 rag/m2 on day 1. Treatment will continue for 6 cycles unless disease progression occurs or toxicity indicates that earlier cessation would be in the pt's best interest. End-points: The main end-point of the trial is response rate assessed by WHO criteria, using CT scanning with tumour measurements at baseline and after every 2 cycles. Additional
end-points are: survival, toxicity (using NCIC common toxicity criteria) and quality of life (QOL). Quality of life is being assessed using the Rotterdam Symptom Checklist questionnaire administered at the start of treatment, before each cycle and at the first two follow-up visits. Fourteen pts will be recruited initially. In the event of a response the number of pts will be increased to 23. If further responses occur, consideration will be given to increasing the numbers to determine the true response rate with smaller confidence intervals. Results: The trial commenced in December 1999 and is recruiting at approximately three patients per month, thus we expect to complete recruitment within six months. Response rates, survival, toxicity and quality of life data from the completed trial will be presented.
•]
Vinorelbine (Navelbine) given as a single agent for malignant pleural mesothelioma. Results from 65 patients at a single
centre J.P.C. Steele, J. Shamash, N.H. Gower, M.T. Evans, M.D. Tischkowitz, R.M. Rudd. St Bartholomew's Hospital, London, UK
Introduction: The incidence of malignant pleural mesothelioma (MPM) is predicted to increase over the next two decades, No chemotherapy is sufficiently effective to be considered as a standard treatment. We recently reported a response rate of >20% in patients with MPM treated with single agent vinoralbine in a phase II study (Proc ASCO 1999; 18: 490). Here we report the response rates and survival data from 65 patients with MPM treated with weekly vinorelbine at our centre. Patients and Methods: Sixty-five patients (pts) with histologicallyproven MPM were enrolled (61 male [94%], 4 female [6%]; median age 59 y [range 29 to 77]; 41 pts had epithelioid tumours, 6 sarcomatoid, 17 b/phasic, one pt had unspecified subtype. International Mesothelioma Interest Group staging: stage h 3 pts; Ih 20; Ill: 19 pts; IV: 22 pts; unspecified: 1 pt. All pts had ECOG perf. status 0-2 and adequate hepatic, renal and haematologic reserve. Vinorelbine 30 mg/m2 was administered weekly for 6 weeks. CT scans were performed after each 6-week block of therapy. Partial response was defined as 50% reduction in b/dimensional area of tumour or 50% reduction in unidimensional transthoracic thickness of tumour according to WHO criteria. An additional level of response ('minor response') was used, defined as ~_ reduction of turnout area or thickness of <50% but >25%. Quality of life was evaluated in all patients with the Rotterdam Symptom Checklist questionnaire. Results: Fifty-eight patients were evaluable for response. There were 12 partial responses (21% [95% confidence interval, 11% to 33%]), 37 pts had stable disease (64%), 9 pts had disease progression on therapy (16%). Of the 37 pts with stable disease, 12 had a minor response to treatment giving a total of 24 pts (41% [95% CI, 29% to 55%]) in whom there was evidence of anti-tumour activity of vinorelbine. The median survival for all 65 pts from date of first treatment was 13.4 months; 57% of pts were alive at one year (95% CI 41% to 71%). Detailed quality of life and toxicity data for all 65 patients will be presented. Summary: A response rate of approximately 20% is encouraging in the setting of MPM. Further trials with vinorelbine or combinations including vinorelbine should be considered. Vinorelbine shows promise in the treatment of pts with MPM.
[•
Multicenter phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma (MPM)
J.W. van Haarst, J.A. Burgers, C.H. Manegold, P. Baas, H. Schouwink, H.G. de Bruin, M.J.A. de Jonge, J.P. van Meerbeeck. University
Hospital Rotterdam, Rotterdam; Netherlands Cancer Institute, Amsterdam; Medisch Spectrum Twente, Enschede, The Netherlands, Thoraxklinik, Heidelberg, Germany Background: MPM is a notoriously chemoresistant tumour. A recent single institution study showed an impressive activity of gemcitabine and cisplatin against MPM (Byrne MJ, JCO 1999; 17: 25-30).
~-0~ls cisplatin necessary for the treatment of non-small cell lung cancer (NSCLC)? - Analysis of consecutive trials of paclitaxel in NSCLC K. Kubota 1, ¥. Nishiwaki 1, A. Yokoyama2, S. Yoneda3, T. Tamura4, K. Watanabe 5, N. Saijo4. 1National Cancer Center Hospital East; 2Niigata Cancer Center Hospital; 3Saitama Cancer Center; 4National Cancer Center Hospital; 5 Yokohama Municipal Citizen's Hospital, Japan Paclitaxel (P) has unique mechanisms of action and is active in NSCLC. Because benefit of combination chemotherapy of P with other agents has not been demonstrated, we conducted an analysis of consecutive trials of P, which included phase II study of P alone and P/cisplatin. In P alone study, 210 mg/m 2 of P was administered as 3-hour infusion and repeated at 21-day interval. Eighty mg/m 2 of cisplatin and 180 mg/m 2 of P (3-hour infusion) were repeated at 21day interval in P/cisplatin study. Eligibility criteria are similar between two studies except for PS (0-2 in P alone, 0-1 in P/cisplatin) and stage (inoperable IIIA/IIIB and IV in P alone, IIIB and IV in P/cisplatin). Baseline demographics of the total 92 patients (pts), response and toxicities are summarized.
No. of pts Median age (range) Male (%) PS 0/1/2 Adeno/Squamous/others IIINIIIB/IV Response rate (%) Neutropenia Grade 3 + 4 (%) Nausea and vomiting (%) Peripheral neuropathy (%)
Paclitaxel alone
Paclitaxel/cisplatin
60 63 (27-74) 45 (75) 14/38/8 41/14/5 5/6/49 38 82 28 70
32 61 (43-:,71) 22 (69) 9/23/27/4/1 -/5/27 31 53 78 47
Survival data will be presented at the meeting. There was no difference in response rate between the two studies. Adding of cisplatin failed to show an advantage over P alone. In conclusion, randomized trials of paclitaxel with or without cisplatin are warranted.
[•
17
Paclitaxel and cisplatin in stage IV non-small cell lung cancer: A GETICS phase II study
A.V. Jaremtchuk, E,E Aman, J.J. Zarba, M Salvadori, R. Alvarez, F. Marmissolle. GETICS, Comodoro Rivadavia; GETICS, Buenos Aires; GETICS, Yerba Buena; GETICS, Santa Rosa; GETICS (Grupo de Estudio Tratamiento e InvestigaciOn del C.ncar del Sur), Argentina
Background: Stage is one of the most important prognostic factors in NSCLC. Unfortunately several studies evaluate chemotherapy regimens in advanced disease pooled stage III and IV patients. Purpose: To evaluate the efficacy, toxicity and survival rate of stage IV NSCLC patients treated with paclitaxel-cisplatin combination. Patients and Methods: Chemotherapy-naive patients with histologically confirmed satge IV NSCLC, ECOG PS 0-1, adequate bone marrow and organ function and measurable disease were eligible for the study. Paclitaxel was administered at a dose of 175 rag/m2, threehour e.v. infusion on day 1 followed by Cisplatin at a dose of 100 rag/m2 with appropriate hydration on day 2. Treatment was repeated every 3 weeks. Results: Thirty-two patients were enrolled, median age was 54 years (range 36 to 74 years). Seventy-five percent of patients were males, 50% had edenocarcinoma and 31% had >10% weight loss. Ninety-one courses were administered and 28 patients received at least two courses of PC regimen. One patient achieved a complete response and 7 patients achieved a partial response for an overall response rate of 25%. The median time to progression, median survival time and one year survival rate were 25 weeks, 41 weeks and 28% respectively. Grade 3/4 leucopenia, thrombocytopenia and anemia were observed in 21%, 6% and 6%. Neuretoxicity grade 2 were observed in 12.5% of patients. No toxic deaths were reported. Conclusion: The data show that paclitaxel plus cisplatin is a welltolerated and active regimen in stage IV NSCLC patients,
15-• Phase II study of paclitaxel, ifosfamide and carboplaUn with fllgrastim support in advanced non-small cell lung cancer (NSCLC)
A.M. Mauer, R.H. Ansari, P.C. Hoffman, T.G. Gabrys. University of Chicago Phase II Network, Chicago, IL, USA Based on the activity observed with the doublet combinations of paclitaxel/carboplatin and paclitaxel/ifosfamide (Annals Oncol 1996, 7: 314-6) in NSCLC, we undertook a phase II study of the triplet combination of paclitaxel, ifosfamide, and carboplatin in patients with advanced NSCLC. Doses and schedule of therapy were based upon phase I study of the triplet regimen completed at our institution. The regimen included paclitaxel (200 mg/m2 per 1 hour on day 1), carboplatin (AUC = 5 on day 2), and ifosfamicle (1500 mg/m2 on days 1 & 2) with Mesna (300 mg/m2 on days 1 & 2) with prophylactic filgrastim support starting on day 4 until ANC > 10,000. Eligibility criteria included stage IIIB (pleural efffusion)/IV NSCLC, measurable disease, normal bone marrow, hepatic, renal function. Patients were allowed to have to have one prior therapy with an investigational agent. Asymptomatic brain metastases were allowed. Fifty patients received protocol therapy. Pt characteristics: male-32; female-18; median age 62; median CALGB performance status-I; stage IIIB-8/IV-42; prior single agent experimental chemotherapy-I; prior chest radiotherapy-2. Median number of cycles administered was 4. Grade 4 hematologic toxicity included thrombocytopenia (6 pts) and neutropenia (7 pts) with neutropenic fever in 1 patient. Non-hematologic toxicity grade > 3 included: vomiting (3 pts), reversible azotemia (grade 3-1 pt), peripheral neuropathy (5 pts) and neurocortical (2 pts). Out of the 42 patients assessed for response, 10 partial responses were noted for an overall response rate of 24%. At a median follow up time of 11.3 months, the median survival is 13.4 months. This large phase II study confirms the feasibility and activity of this triplet regimen in patients with advanced non-small cell lung cancer.
18
Chemotherapy/Mesotheliome
Wednesday, 13 September 2000
10:30-12:00
ORAL SESSION
Chemotherapy/Mesotheliome
•
Combined treatment of malignant mssothelioma (MM) of the pleura with high dose Methotrexate (Mtx), and interferons alfa (IFA) and gamma (IFG)
O. Brodin, A. Knuuttila, M. Halme, H. Strander, C.J. LindEn, G. Hillerdal, K. Mattsson. Oncology, South Hospital, Stockholm;
Radiumhemmet, Karolinska Hospital, Stockholm; Medicine, University Hospital, Lund; Lung Medicine, University Hospital, Uppsala, Sweden, Medicine, University Central Hospital, Helsinki, Finland Median survival of patients with MM has been reported to be only 9-12 months. A response-rate of 37% has been reported for high dose Mtx. Also treatments with sc IFA and intraperitoneally IFG have accomplished responses (12% and 24%, respectivelly). We hoped to improve treatment result further by combining all three drugs. Patients with verified MM stage II-IV were included in this mutticentric phase II study. Marker lesions were identified on CT-scan taken before start of treatment and followed during and after treatment. Treatment consisted of Mtx given at a total dose of 3000 mg in each patient, together with Leucovorin rescue for totally 6 courses. IFA was given sc 3 milj IE for 8 days between each course and IFG 40 mikrog at 3 occasions between each course. After cessation of MTX, the IFA and IFG treatments proceeded at lower dosage. Forty-six patients were included. Responses, all partial, were found in 12 patients (27%). Toxicity was mainly haematological. No lethal toxicity was registered. Preliminarily, median survival is 13 months. The respons rate with these three drugs was worse than that reported with solely Mtx. If this was due to differences in response evaluation, if the 3 drugs interacted subtractively or if random factors have influenced the result, is an open question. Besides, this combined treatment was complicated and expensive and there is no indication that it improved median survival.
~ - ] Phase II trial of vinorelbine and oxaliplatin in patients with malignant pleural mesothelioma J.P.C. Steele, J. Shamash, M.T. Evans, N.H. Gower, RM. Rudd. St Bartholomew's Hospital, London, UK Introduction: The increasing incidence of malignant pleural mesothelioma (MPM) in Europe has led to renewed effort in the search for effective treatments for this poor-prognosis disease. We recently reported encouraging response rates in a phase II trial with single-agent vinorelbine (Proc ASCO 1999: 18: 490). This data prompted further examination of this semi-synthetic vinca alkaloid in combination with the new-generation platinum agent oxaliplatin. The apparent synergy between vinorelbine and platinum agents makes this a logical next step. Treatment Plan: We are examining the efficacy of the combination of vinorelbine (Navelbine, Pierre Fabra, France) and oxaliplatin (EIoxat/n, Sanofi, France) in an open phase II study in patients (pts) with previously untreated MPM. Entry criteria include: ECOG performance status of 0-2; measurable or evaluable disease; adequate hepatic, renal and haematologic reserve for platinum-based treatment. Pts with medical conditions that preclude the use of chemotherapy; active infection; brain metastases; or a history of prior malignancy are excluded. Treatment involves the intravenous administration of vinorelbine 30 rag/m2 on days 1 and 8 of a 21-day cycle and oxaliplatin 130 rag/m2 on day 1. Treatment will continue for 6 cycles unless disease progression occurs or toxicity indicates that earlier cessation would be in the pt's best interest. End-points: The main end-point of the trial is response rate assessed by WHO criteria, using CT scanning with tumour measurements at baseline and after every 2 cycles. Additional
end-points are: survival, toxicity (using NCIC common toxicity criteria) and quality of life (QOL). Quality of life is being assessed using the Rotterdam Symptom Checklist questionnaire administered at the start of treatment, before each cycle and at the first two follow-up visits. Fourteen pts will be recruited initially. In the event of a response the number of pts will be increased to 23. If further responses occur, consideration will be given to increasing the numbers to determine the true response rate with smaller confidence intervals. Results: The trial commenced in December 1999 and is recruiting at approximately three patients per month, thus we expect to complete recruitment within six months. Response rates, survival, toxicity and quality of life data from the completed trial will be presented.
•]
Vinorelbine (Navelbine) given as a single agent for malignant pleural mesothelioma. Results from 65 patients at a single
centre J.P.C. Steele, J. Shamash, N.H. Gower, M.T. Evans, M.D. Tischkowitz, R.M. Rudd. St Bartholomew's Hospital, London, UK
Introduction: The incidence of malignant pleural mesothelioma (MPM) is predicted to increase over the next two decades, No chemotherapy is sufficiently effective to be considered as a standard treatment. We recently reported a response rate of >20% in patients with MPM treated with single agent vinoralbine in a phase II study (Proc ASCO 1999; 18: 490). Here we report the response rates and survival data from 65 patients with MPM treated with weekly vinorelbine at our centre. Patients and Methods: Sixty-five patients (pts) with histologicallyproven MPM were enrolled (61 male [94%], 4 female [6%]; median age 59 y [range 29 to 77]; 41 pts had epithelioid tumours, 6 sarcomatoid, 17 b/phasic, one pt had unspecified subtype. International Mesothelioma Interest Group staging: stage h 3 pts; Ih 20; Ill: 19 pts; IV: 22 pts; unspecified: 1 pt. All pts had ECOG perf. status 0-2 and adequate hepatic, renal and haematologic reserve. Vinorelbine 30 mg/m2 was administered weekly for 6 weeks. CT scans were performed after each 6-week block of therapy. Partial response was defined as 50% reduction in b/dimensional area of tumour or 50% reduction in unidimensional transthoracic thickness of tumour according to WHO criteria. An additional level of response ('minor response') was used, defined as ~_ reduction of turnout area or thickness of <50% but >25%. Quality of life was evaluated in all patients with the Rotterdam Symptom Checklist questionnaire. Results: Fifty-eight patients were evaluable for response. There were 12 partial responses (21% [95% confidence interval, 11% to 33%]), 37 pts had stable disease (64%), 9 pts had disease progression on therapy (16%). Of the 37 pts with stable disease, 12 had a minor response to treatment giving a total of 24 pts (41% [95% CI, 29% to 55%]) in whom there was evidence of anti-tumour activity of vinorelbine. The median survival for all 65 pts from date of first treatment was 13.4 months; 57% of pts were alive at one year (95% CI 41% to 71%). Detailed quality of life and toxicity data for all 65 patients will be presented. Summary: A response rate of approximately 20% is encouraging in the setting of MPM. Further trials with vinorelbine or combinations including vinorelbine should be considered. Vinorelbine shows promise in the treatment of pts with MPM.
[•
Multicenter phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma (MPM)
J.W. van Haarst, J.A. Burgers, C.H. Manegold, P. Baas, H. Schouwink, H.G. de Bruin, M.J.A. de Jonge, J.P. van Meerbeeck. University
Hospital Rotterdam, Rotterdam; Netherlands Cancer Institute, Amsterdam; Medisch Spectrum Twente, Enschede, The Netherlands, Thoraxklinik, Heidelberg, Germany Background: MPM is a notoriously chemoresistant tumour. A recent single institution study showed an impressive activity of gemcitabine and cisplatin against MPM (Byrne MJ, JCO 1999; 17: 25-30).