Limited Disease Small Cell Lung Research Articles

P-58 Phase II study of irinotecan/cisplatin (IP) induction chemotherapy followed by concurrent twice-daily thoracic radiotherapy (RT) with etoposide/cisplatin (EP) for limited disease small cell lung cancer (LD-SCLC)

P-58 Phase II study of irinotecan/cisplatin (IP) induction chemotherapy followed by concurrent twice-daily thoracic radiotherapy (RT) with etoposide/cisplatin (EP) for limited disease small cell lung cancer (LD-SCLC)

P-55 Chemotherapy with ifosfamide and concomitant radiotherapy in limited disease (LD) small cell lung cancer (SCLC)

A restrospective study of 115 consecutive pts. with limited SCLC was aimed at therapeutic results and toxicity. From preliminary results authors conclude that the use of IFO/CBDCA/VP16 with concomitant raditherapy is an effective therapy, radiotherapy reducing the treatment time.

Surgical treatment of small cell lung cancer

Chemoradiotherapy remains a gold standard in the treatment of limited-disease small cell lung cancer. Currently, three indications for the surgical treatment of very limited disease (stage I, II, or highly selected IIIa) small cell lung cancer can be identified: (1) primary surgery in peripheral clinical N0 lesions followed by adjuvant chemotherapy or chemoradiotherapy; (2) primary chemotherapy or chemoradiotherapy followed by surgery +/− radiotherapy in patients with a good response to initial treatment; and (3) salvage operations in patients who recur or persist at the primary site but still have resectable disease. The value of these approaches has been assessed in retrospective analyses and prospective nonrandomized trials. A large prospective randomized trial failed to prove any added value for surgery in the multidisciplinary treatment of limited-disease small cell lung cancer, but very few very-limited-disease patients were included. Semin Oncol 30:47-56. Copyright 2003, Elsevier Science (USA). All rights reserved.

180. The role of surgery in management of limited disease (LD) small cell lung cancer (SCLC), a retrospective comparative study

To asses the role of surgery in SCLC we performed a retrospective analysis of survival in two groups of LD patients (pts) treated between 1982 and 1995. In one group (67 pts) complete resection was followed by chemotherapy, the other (67 pts) was treated with conventional nonsurgical management. In all operated pts the diagnosis of SCLC was established only after the examination of surgical specimen. The non-surgical group was selected using “pair-matched case-control” methodology out of 176 LD pts potentially suitable for surgery (i. e. no pleural effusion or other local advancement, no supraclavicular lymph node involvement, good PS) but treated with non-surgical approach. Total series included 109 males and 25 females, 20 T1 and 114 T2 disease, 51 N0, 43 N1 and 40 N2 disease. In the surgical group 23 pts received prophylactic cranial irradiation and in the non-surgical group 39 pts received thoracic irradiation. The most important prognostic factors were well balanced between both groups. Median survival in pts treated with and without surgery was 22 months and 11 months, respectively (p

Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: A randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG)

Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response. 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded. Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.

The role of surgery in limited disease (LD) small cell lung cancer (SCLC): a retrospective, comparative study

The role of surgery in limited disease (LD) small cell lung cancer (SCLC): a retrospective, comparative study

Phase II trial of high dose chemotherapy with amifostine and concurrent irradiation in limited disease small cell lung cancer (SCLC)

Phase II trial of high dose chemotherapy with amifostine and concurrent irradiation in limited disease small cell lung cancer (SCLC)

A retrospective comparative study of surgery followed by chemotherapy (CT) vs. non-surgical management in limited disease (LD) small cell lung cancer (SCLC)

A retrospective comparative study of surgery followed by chemotherapy (CT) vs. non-surgical management in limited disease (LD) small cell lung cancer (SCLC)

Combination chemotherapy with low doses of weekly Carboplatin and oral Etoposide in poor risk small cell lung cancer

Sixty patients with poor prognostic features, either with extensive disease (ED) or limited disease (LD) small cell lung cancer (SCLC), were treated on an out-patient basis with Carboplatin 80 mg/m 2 weekly for 3 weeks and oral Etoposide, at a dose of 100 mg, every other day for 21 days. The treatment was repeated every 5 weeks. Responding patients with LD were also treated with thoracic irradiation and those who achieved complete response (CR) received prophylactic cranial radio-therapy. The overall response rate (RR) was 32.1% with 8.9% CR. The responses were better for LD (RR 58.3%, CR 25%, partial response, PR 33.3%), than those for ED (RR 25%, CR 4.5%, PR 20.5%). The median time to progression (TTP) was 4.8 months and the median survival 5.5 months. These poor results could be attributed to the bad performance status and the presence of visceral and brain metastases in this group of patients. The results could also be due to the lower maximum concentration (C max) and higher T 1/2 of Etoposide, as measured in the blood and urine probably due to the modified regimen used in our study and to the organ insufficiency in this selected group of patients. Although, toxicity was generally mild and manageable, two toxic deaths occurred. In conclusion, this regimen appears to have a lower efficacy in terms of response and survival than that obtained in other studies using Cisplatin or Carboplatin plus Etoposide in a similar way. Therapy with this regimen, though less toxic, may not be a reliable alternative in elderly patients with visceral metastases and ECOG performance status ≥2.

Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

Integration of filgrastim into chemoradiation for limited small cell lung cancer: A phase I study

Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) +/- filgrastim (5 microg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1-3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). Despite careful attention to the timing of growth factor with chemoradiation, the administration of filgrastim with this regimen did not allow dose escalation. As in many other recent studies of hematopoietic growth factors given prophylactically with chemotherapy, the duration of neutropenia at the MTD was shortened and the need for dose reduction throughout treatment was reduced in patients receiving filgrastim at the MTD.

235 Preliminary results of a stage orientated multimodality treatment including surgery for selected subgroups of limited disease small cell lung cancer (SCLC)

235 Preliminary results of a stage orientated multimodality treatment including surgery for selected subgroups of limited disease small cell lung cancer (SCLC)

168 A pilot study of high dose chemotherapy and irradiation with NEUPOGEN (G-CSF) in limited disease small cell lung cancer (SCLC)

168 A pilot study of high dose chemotherapy and irradiation with NEUPOGEN (G-CSF) in limited disease small cell lung cancer (SCLC)

504 Early vs late bifractionated chest irradiation concurrently with chemotherapy in limited disease (LD) small-cell lung cancer (SCLC) (Preliminary results)

504 Early vs late bifractionated chest irradiation concurrently with chemotherapy in limited disease (LD) small-cell lung cancer (SCLC) (Preliminary results)

86 Preliminary results of a stage oriented multimodality treatment including surgery for selected subgroups of limited disease small cell lung cancer (SCLC)

Since 6/91, 38 patients (pts) with limited disease SCLC (mediastinoscopy obligatory) have been entered into this ongoing trial. Pts with stage, I and II were treated with 4 cycles cisplatin (50 mg/m 2 d 1 + 7) and etoposide (170 mg/m 2 d 3, 4, 5) = PE, q d 22 followed by restaging and surgery. IIIa pts were treated with 3 cycles of PE, q d 22 followed by one cycle simultaneous RTx/CTx (45 Gy, 1,5 Gy twice daily within 3 weeks; P 50 mg/m d 2 + 9 of RTx, E 100 mg/m2 d 4, 5, 6 of RTx) followed by remediastinoscopy and operation. III b pts were treated with 4 cycles PE q d 22 followed by sequential RTx or 3 cycles PE plus 1 cycle of PE with simultaneous RTx (50 Gy, conventional fractionation, 2 Gy daily for 5 weeks). Pts characteristics m/f 26/12; age 55 (34–69); PS 1 (0–1); Stage I6, II2, IIIa 17, IIIb 13. Results after CTx +/− RTx cCR 14; PR 21, CR/PR 35 (92%), MR 2. TOXICITY (WHO): lucopenia 3° 25%, 4° 10%; Infection 3 ° 10%, 4° 5%; thrombocytopenia 3°/4° 20%; diarrhea 3° 5%. One pt died of treatment related septicemia. Seventeen out of 25 (68% (stage I 6/6; stage II 2/2; stage IIIA 9/17)) pts underwent R0 resection including 7 (28%) pCR's. So far CNS relapses were the only site of failure in 7/17 pts who had RO resection. None of them failed locoregionally. The median observation time for pts alive is 15 (3–46) months (MTS). The median survival for all 38 pts is 29 (3+–46+) MTS; stage I–III A not yet reached (3+–46+ MTS), and RO resection not yet reached (5+–46+ MTS, 71% at 27 MTS); stage IIIB 15 (6+–35+) MTS. Conclusions This intensive stage oriented multimodailty program is tolerable and highly effective for LD SCLC. Of note is the high local tumor control rate (100%) of pts with stage I-IIIA who underwent R0 resection.

Early alternating chemotherapy and radiotherapy schedule in limited disease stage small cell lung cancer.

44 patients with limited small cell lung cancer were treated with six cycles of chemotherapy (cisplatinum 60 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, etoposide 100 mg/m2 days 1-3) alternating with three courses of mediastinal irradiation, the first one starting 7 days after the first day of chemotherapy. A total dose of 55 Gy was delivered. Prophylactic cranial irradiation (30 Gy after the third cycle of chemotherapy) was left to the physician's discretion. 4 patients had radical surgery before combined modality treatment. 29 patients finished the scheduled program. The complete response rate (bronchoscopically confirmed) was 25.6% after two cycles of chemotherapy and 41% at the end of treatment. Median survival time was 17.2 months, with an estimated survival of 32% at 2 years. Main toxicity was haematological with one early toxic death and six premature interruptions of treatment. We conclude that this treatment modality is feasible and efficacious. Prospective studies comparing chemotherapy with alternating or concurrent early radiotherapy schedules in limited disease small cell lung cancer are needed to determine the best treatment modality.

Preliminary results of a prognostically/stage orientated multimodality treatment including surgery for selected subgroups of limited disease small cell lung cancer (SCLC) : W.Eberhardt, H.Wilke, G.Stamatis, S.Kolks,M.Stuschke, M. Stahl, G.Trenn, U. Vanhoefer, M.R. Müller, L..Schlenger, M.R. Nowrousian, D. Greschuchna, N. Konietzko,and S.Seeber. Dept. Int. Med. (Cancer Res.), Essen University Medical School, Essen, Germany

Preliminary results of a prognostically/stage orientated multimodality treatment including surgery for selected subgroups of limited disease small cell lung cancer (SCLC) : W.Eberhardt, H.Wilke, G.Stamatis, S.Kolks,M.Stuschke, M. Stahl, G.Trenn, U. Vanhoefer, M.R. Müller, L..Schlenger, M.R. Nowrousian, D. Greschuchna, N. Konietzko,and S.Seeber. Dept. Int. Med. (Cancer Res.), Essen University Medical School, Essen, Germany

Consolidative thoracic radiotherapy and prophylactic cranial irradiation in limited disease small cell lung cancer

Between 1983 and 1990, 128 patients with limited disease small cell lung cancer (SCLC) received consolidative thoracic irradiation after reaching a complete (CR) or partial response (PR) to combination chemotherapy. Patients in CR ( n = 85) received 35–36 Gy in 12–14 fractions and patients in PR ( n = 43) 24–30 Gy in 3–6 fractions. Until 1989, prophylactic cranial irradiation (PCI) was given to patients in CR. There was no significant difference in survival between the CR and PR group. However, patients with residual tumor detected by radiology or bronchoscopy or cyto-/histology had significantly longer survival than those with residual tumor demonstrated by more than one of the above methods of investigation. Overall, local progression was observed in 22% and distant dissemination in 63% of patients. The rate of brain metastases was significantly lower in patients treated with methotrexate and nitrosurea containing schedules and PCI, compared to those who were treated with other schedules (irrespective of PCI).

Limited disease small cell lung cancer: alternating combination of doxorubicin, etoposide, ifosfamide and hyperfractionated radiotherapy: Final results of a multicentric pilot study from the Groupe Lyonnais d'Oncologie Thoracique (GLOT)

In order to evaluate the effect on prolonging survival of alternating chemotherapy and radiotherapy schedules in patients with limited disease small cell lung cancer, 89 patients were included in a multi-institutional pilot study between January 1986 and May 1989. Treatment consisted of induction chemotherapy using the combination of doxorubicin, etoposide and ifosfamide (AVI) for four consecutive courses, followed by two cycles of the VI chemotherapy alternating with three hyperfractionated radiotherapy courses and then followed by two additional courses of AVI. Objective response to the four cycles of AVI combination was observed in 65 patients (75%). Thirteen out of 30 patients (44%) who were in partial response (PR) after induction chemotherapy were converted into complete response (CR) after the three alternating courses of chemotherapy and radiotherapy. The principal side effect related to combined modality treatment was acute radiation pneumonitis (21.5% cases) reversible except one which resulted in toxic death, and a second with chronic lung fibrosis with permanent WHO Grade 2 dyspnea (14%). Local relapse was observed in 47% of the patients who were considered in CR at the end of the treatment program and cerebral metastases were the first site of detectable relapse in 25% cases. The 3-year actuarial disease-free survival of the 89 patients is 5%, and the median actuarial survival is 14 months. This study shows that the promising survival rates seen in our previously published interim analysis were not maintained. Reasons for this might include the choice of a non cisplatinum containing induction chemotherapy, the late introduction of thoracic irradiation and/or to the use of non-restrictive criteria for selecting patients.

Morphology, surface antigens, staging, and prognostic factors of small cell lung cancer.

Morphologic as well as biologic properties of small cell lung cancer change under chemotherapy toward a non-small cell and well-differentiated neuroendocrine phenotype. These biologic changes may be partly responsible for the acquisition of drug resistance. With the lack of significant advances with currently available chemotherapy, the development of new treatment strategies has become a major focus of research. Among others, these could include the use of antibodies to small cell lung cancer antigens. Several antigens associated with small cell lung cancer have now been biochemically and molecularly defined in the International Workshop of Small Cell Lung Cancer Antigens. In vitro and in vivo models have demonstrated the selective cytotoxic effect of immunoconjugates with radionuclides and plant toxins. Since recent clinical studies suggested a survival advantage for the use of radiotherapy in limited disease small cell lung cancer, anatomical staging to exclude distant sites of metastasis is likely to continue in clinical practice. Studies with a focus on cost-effective ways of anatomic staging are therefore of great importance. Continued efforts are under way to analyze pretreatment prognostic factors. The likely association of female gender with good prognosis and the in vitro data on stimulation of proliferation of small cell lung cancer cells by androgens may lead to the investigation of new therapeutic approaches based on endocrine manipulation.