- Email: [email protected]
Palliation and quality of life after hypofractionated radiotherapy (500 cGy × 12) plus Vinorelbine (NVB) in stage IIIA–B NSCLC patients
Combined Modality Therapy~Small
•
Population-based outcome for small cell lung cancer (SCLC): Impact of standard management policies in British Columbia (BC)
N. Murray, A. Coldman, Y. D'yachkova, C. Trevisan, I. Olivotto, G. Hislop. British Columbia Cancer Agency (BCCA), Vancouver,
Canada Survival data for SCLC is typically reported from clinical trials or institutional series where patients were fit enough to meet treatment criteria. The denominator of all SCLC patients from which the treated population is derived is rarely reported. In BC (population 3.7 million), the BCCA is a single centralized cancer agency that develops and circulates province-wide treatment guidelines, and coordinates cancertreatment services in the province. The BC Cancer Registry was used to identify all cases of SCLC in two years: 331 cases in 1990 and 297 cases in 1995. Demographic, staging, treatment, and followup details were abstracted from cancer centre records or primary physicians for 100% of cases. Seventy-one of 628 (11.3%) were terminally ill (<2 wk survival) or had an autopsy diagnosis. Twenty percent (112/557) of patients surviving >2 wks did not receive any chemotherapy (CT). Reasons cited for no CT in 112 patients included: patient refusal (43), poor performance status (31), centraindication (10), and other (21). Advanced age was the principal reason for not receiving CT in only 7 cases.
Group
Total (%)
All All (survived >2 wks)
628 557 (88.7%) Received any CT 445/557 (80%) Extensive Stage (CT) 278/359 (77%) Limited Stage ( C T ) 167/198 (84%) Limited (XRT + CT) 137/167 (82%)
Median survival (mos)
Survival (%) 2-year
4-year
7.3 8.7
11.4 12.9
4.7 5.3
10.7
15.4
6.4
8.6
7.6
3.2
13.4
25.0
9.8
15.3
32.7
13.8
Conclusion: This analysis of SCLC shows that only 71% of the entire patient population are amenable to standard treatment policies. Eleven percent are terminally in at diagnosis and 20% will not receive CT for other reasons. Only 137/628 (22%) were treated with combined modality therapy with curative intent. A realistic estimate of the impact of therapy innovations on population-based outcome must consider the likelihood of treatment delivery for the entire SCLC patient population.
•1-•
Early concurrent chemotherapy with carboplatinletoposide plus normofractionated radiotherapy in limited stage small cell lung cancer (SCLC)
Z. Skacel, M Marel, J. Prausov& J. Hovorkov& R. Pipkov& L. Melinov& K. Ko.~atova, B. St'astn~. Pneumological Dept.,
Radiologic Dept. and Radiotherapeutic Dept. University Hospital Motol, Pneumological Clinic, Prague, Czech Republic Early concurrent platinum-based chemoradiotherapy may improve survival in limited SCLC compared to sequential chemoradiation. In our phase II trial we evaluated efficacy and toxicity of carboplatin/etoposide regimen given concurrently with thoracic radiotherapy. Chemotherapy was given in following scheme: 5 courses of carboplatin AUC = 6 day 1 + etoposide 100 mg/m 2 day 1,2, 3 q 21 days plus radiotherapy 1,8 Gy once daily 5 days/week to a total dose of 45 Gy starting from the 1st day of 2nd course of chemotherapy. PC130 Gy after the 5th course was given to patients with CR or major PR. Inclusion criteria: histologically
97
or cytologically prooven limited SCLC without previous chemotherapy or radiotherapy, age bellow 65 years, PS 0-1, adequate renal, hepatic and haematologic values. Results: So far, 12 patients (9 males, 3 females) have entered the trial (3 stage IliA, 9 stage IIIB), 8 are currently evaluable for response and toxicity. Overall response: CR6/8, PR 1/8. With median follow-up of 10 months, all patients are alive, there is only one (CNS) recurrence. Toxicity: totally 38 cycles were administered, haematologic: leucopenia gr. Ill/IV: 4/1 cycles, neutropenia gr. Ill/IV: 4/3 cycles, thrombocytopenia gr. Ill/IV: 1/1 cycles. Nonhaematologic toxicity: pneumonitis gr. Ill/IV: 1/0 patient, esophagitis gr. Ill/IV: 1/0 patient. Conclusion: This treatment is highly active and little toxic. We suppose following reasons for low toxicity: use of cerboplatin instead of cisplatin, use of conformal 3-D radiotherapy and its start from the 2nd cycle of chemotherapy what allows diminishing of irradiated area.
I - ~ ~ Palliation and quality of life after hypofractionated radiotherapy (500 cGy x 12) plus Vinorelbine (NVB) in stage IIIA-B NSCLC patients G. Silvano, S. Campoccia, S. Colosimo, S. Moda. Oncology
Department - Radiation Therapy Division, Pisa, ITALY Palliative treatment of NSCLC involves more than 50% of patients, usually treated with radiation therapy (RT) and/or chemotherapy (CT). Single-agent NVB provides survival benefits comparable with more aggressive and toxic regimens and demonstrated the potentiation of RT in experimental studies. To optimise cost-effectiveness and toxicity we proposed hypofractionated RT (hRT) plus NVB in a phase 1/11study (SOMPS, Paris, 1996). Ten patients affected by NSCLC, stage IlIA-B, unsuitable for curative RT and for cisplatin-based CT, were enrolled to receive 10-15-20 mg/m2 of NVB weekly for 12 cycles plus chest hRT 500 cGy/fraction 6-8 hours before NVB infusion. Opposed APPA fields or multiple fields were used not exceeding 225 cm2 each. Quality of life questionnaires based on Spitzer QL-Index were compiled baseline, each 3 weeks till the end of hRT and every two months until progression. Males were 9/10, ECOG PS was 1-3, median age was 70 years (52-75). The most frequent symptoms were dyspnea, cough and chest pain: their intensity was classified high or medium in 60%, 80% and 60% of patients respectively. Four patients received NVB 10 mg/m2 and 6 patients received 15 mg/m2. In the first group 3/4 (75%) of patients completed 6 or more cycles of NVB plus hRT: 1 patient stopped because impairment of neurological functions not treatment related. In the second group 4 patients out of six (66.6%) received at least 6 cycles of NVB plus hRT: treatment was interrupted because progressive disease (1 patient) and because myelosuppression (1 patient). In the 10 mg/m2 group we observed late esophagitis and pneumonitis as grade 3 WHO toxicity, in the same patient. In the second group we observed, as grade 3 not haematological toxicity, asthenia in 2 patients, pneumonitis in 1 patient, lung fibrosis in 1 patient. As grade 3-4 haematological toxicity we observed leukopenia in 2 patients and anaemia in 1 patient. After six cycles of NVB and hRT only cough was still present in 2/10 patients (20%) while dyspnea and chest pain were controlled. Quality of life questionnaires were returned by 8/10 patients. Comparing the first and the last tests, we did not observe any significant variation of Spitzer QL-Index scores. We conclude that: 1) maximum tolerated dose of NVB according to the our schedule plus hRt is 10 mg/m2; 2) hRT plus NVB gives good symptoms control but does not improve quality of life because toxicity observed in patients treated with 15 mg/m2 of NVB.
•
Population-based outcome for small cell lung cancer (SCLC): Impact of standard management policies in British Columbia (BC)
N. Murray, A. Coldman, Y. D'yachkova, C. Trevisan, I. Olivotto, G. Hislop. British Columbia Cancer Agency (BCCA), Vancouver,
Canada Survival data for SCLC is typically reported from clinical trials or institutional series where patients were fit enough to meet treatment criteria. The denominator of all SCLC patients from which the treated population is derived is rarely reported. In BC (population 3.7 million), the BCCA is a single centralized cancer agency that develops and circulates province-wide treatment guidelines, and coordinates cancertreatment services in the province. The BC Cancer Registry was used to identify all cases of SCLC in two years: 331 cases in 1990 and 297 cases in 1995. Demographic, staging, treatment, and followup details were abstracted from cancer centre records or primary physicians for 100% of cases. Seventy-one of 628 (11.3%) were terminally ill (<2 wk survival) or had an autopsy diagnosis. Twenty percent (112/557) of patients surviving >2 wks did not receive any chemotherapy (CT). Reasons cited for no CT in 112 patients included: patient refusal (43), poor performance status (31), centraindication (10), and other (21). Advanced age was the principal reason for not receiving CT in only 7 cases.
Group
Total (%)
All All (survived >2 wks)
628 557 (88.7%) Received any CT 445/557 (80%) Extensive Stage (CT) 278/359 (77%) Limited Stage ( C T ) 167/198 (84%) Limited (XRT + CT) 137/167 (82%)
Median survival (mos)
Survival (%) 2-year
4-year
7.3 8.7
11.4 12.9
4.7 5.3
10.7
15.4
6.4
8.6
7.6
3.2
13.4
25.0
9.8
15.3
32.7
13.8
Conclusion: This analysis of SCLC shows that only 71% of the entire patient population are amenable to standard treatment policies. Eleven percent are terminally in at diagnosis and 20% will not receive CT for other reasons. Only 137/628 (22%) were treated with combined modality therapy with curative intent. A realistic estimate of the impact of therapy innovations on population-based outcome must consider the likelihood of treatment delivery for the entire SCLC patient population.
•1-•
Early concurrent chemotherapy with carboplatinletoposide plus normofractionated radiotherapy in limited stage small cell lung cancer (SCLC)
Z. Skacel, M Marel, J. Prausov& J. Hovorkov& R. Pipkov& L. Melinov& K. Ko.~atova, B. St'astn~. Pneumological Dept.,
Radiologic Dept. and Radiotherapeutic Dept. University Hospital Motol, Pneumological Clinic, Prague, Czech Republic Early concurrent platinum-based chemoradiotherapy may improve survival in limited SCLC compared to sequential chemoradiation. In our phase II trial we evaluated efficacy and toxicity of carboplatin/etoposide regimen given concurrently with thoracic radiotherapy. Chemotherapy was given in following scheme: 5 courses of carboplatin AUC = 6 day 1 + etoposide 100 mg/m 2 day 1,2, 3 q 21 days plus radiotherapy 1,8 Gy once daily 5 days/week to a total dose of 45 Gy starting from the 1st day of 2nd course of chemotherapy. PC130 Gy after the 5th course was given to patients with CR or major PR. Inclusion criteria: histologically
97
or cytologically prooven limited SCLC without previous chemotherapy or radiotherapy, age bellow 65 years, PS 0-1, adequate renal, hepatic and haematologic values. Results: So far, 12 patients (9 males, 3 females) have entered the trial (3 stage IliA, 9 stage IIIB), 8 are currently evaluable for response and toxicity. Overall response: CR6/8, PR 1/8. With median follow-up of 10 months, all patients are alive, there is only one (CNS) recurrence. Toxicity: totally 38 cycles were administered, haematologic: leucopenia gr. Ill/IV: 4/1 cycles, neutropenia gr. Ill/IV: 4/3 cycles, thrombocytopenia gr. Ill/IV: 1/1 cycles. Nonhaematologic toxicity: pneumonitis gr. Ill/IV: 1/0 patient, esophagitis gr. Ill/IV: 1/0 patient. Conclusion: This treatment is highly active and little toxic. We suppose following reasons for low toxicity: use of cerboplatin instead of cisplatin, use of conformal 3-D radiotherapy and its start from the 2nd cycle of chemotherapy what allows diminishing of irradiated area.
I - ~ ~ Palliation and quality of life after hypofractionated radiotherapy (500 cGy x 12) plus Vinorelbine (NVB) in stage IIIA-B NSCLC patients G. Silvano, S. Campoccia, S. Colosimo, S. Moda. Oncology
Department - Radiation Therapy Division, Pisa, ITALY Palliative treatment of NSCLC involves more than 50% of patients, usually treated with radiation therapy (RT) and/or chemotherapy (CT). Single-agent NVB provides survival benefits comparable with more aggressive and toxic regimens and demonstrated the potentiation of RT in experimental studies. To optimise cost-effectiveness and toxicity we proposed hypofractionated RT (hRT) plus NVB in a phase 1/11study (SOMPS, Paris, 1996). Ten patients affected by NSCLC, stage IlIA-B, unsuitable for curative RT and for cisplatin-based CT, were enrolled to receive 10-15-20 mg/m2 of NVB weekly for 12 cycles plus chest hRT 500 cGy/fraction 6-8 hours before NVB infusion. Opposed APPA fields or multiple fields were used not exceeding 225 cm2 each. Quality of life questionnaires based on Spitzer QL-Index were compiled baseline, each 3 weeks till the end of hRT and every two months until progression. Males were 9/10, ECOG PS was 1-3, median age was 70 years (52-75). The most frequent symptoms were dyspnea, cough and chest pain: their intensity was classified high or medium in 60%, 80% and 60% of patients respectively. Four patients received NVB 10 mg/m2 and 6 patients received 15 mg/m2. In the first group 3/4 (75%) of patients completed 6 or more cycles of NVB plus hRT: 1 patient stopped because impairment of neurological functions not treatment related. In the second group 4 patients out of six (66.6%) received at least 6 cycles of NVB plus hRT: treatment was interrupted because progressive disease (1 patient) and because myelosuppression (1 patient). In the 10 mg/m2 group we observed late esophagitis and pneumonitis as grade 3 WHO toxicity, in the same patient. In the second group we observed, as grade 3 not haematological toxicity, asthenia in 2 patients, pneumonitis in 1 patient, lung fibrosis in 1 patient. As grade 3-4 haematological toxicity we observed leukopenia in 2 patients and anaemia in 1 patient. After six cycles of NVB and hRT only cough was still present in 2/10 patients (20%) while dyspnea and chest pain were controlled. Quality of life questionnaires were returned by 8/10 patients. Comparing the first and the last tests, we did not observe any significant variation of Spitzer QL-Index scores. We conclude that: 1) maximum tolerated dose of NVB according to the our schedule plus hRt is 10 mg/m2; 2) hRT plus NVB gives good symptoms control but does not improve quality of life because toxicity observed in patients treated with 15 mg/m2 of NVB.