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PubMedDate not supplied

Prognostic factors in Greek patients with small cell lung cancer (SCLC). A Hellenic Cooperative Oncology Group study.

BACKGROUND: Prognostic factors among Greek patients with SCLC were evaluated. PATIENTS AND METHODS: Data from 516 patients with SCLC treated by the Hellenic Cooperative Oncology Group were analyzed. Multivariate analysis was performed. RESULTS: Complete response (CR) was achieved in 26.8% and partial response in 40.1% of patients. The median duration of response was 7.4 months, the median survival 10.5 months and the 2-year survival rate 12%. The stage of the disease was a dominant prognostic factor for survival and response. PS 0-1 was a major prognostic factor for survival, duration of response and CR. Female gender was a favorable predictor for CR. Superior vena cava syndrome was a poor prognostic factor for survival and duration of response. Weight loss and age > or = 60 were poor predictors for response. The sites of metastases affected survival, duration of response and response. Normal alkaline phosphatase was a favorable prognostic factor for survival, duration of response and response. Normal lactate dehydrogenase and thoracic irradiation were favorable prognostic factors for survival and duration of response.

Adult↗

PubMed2003

[Prognosis in limited disease (LD) small cell lung cancer (SCLC) patients according to status performance, local extension of lesions, type of treatment and the completeness of staging].

The aim of this study was to assess the prognosis in LD SCLC pts according to their performance status, local extension of lesions, type of treatment and the completeness of staging. In the period 01.01.1986-31.12.1996 in the Institute of Tuberculosis and Chest Diseases 579 consecutive SCLC pts were treated. LD was diagnosed in 345 pts. In 193 out of them the staging was complete that is in addition to chest x-ray, abdomen USG/CT, brain CT/MRI and bilateral bone marrow trepanobiopsy was done. 152 pts were also regarded as limited but the staging was not complete. LD pts proved by complete staging survived significantly longer (median survival 15.7 months) than others (median survival 10.2 months). The pts in whom complete staging was done were however in better performance status and had smaller local extension of lesions and had more often radiotherapy than others. Status performance, local extension of lesions and radiotherapy but also completeness of staging were independent prognostic factors in multivariate analysis.

Adult↗

PubMed1991

Selection of anti-SCLC antibodies for diagnosis of bone marrow metastasis.

The binding profile of 17 monoclonal antibodies (MAbs) to small lung cancer cell lines and normal bone marrow and peripheral blood cells was studied by immunocytochemistry and flow cytometry. At antibody concentrations that stained PJD tumour cells, only four MAbs (MOC1, MOC31, NrLu10, 81A6) were devoid of cross-reactivity with normal cells, whereas significant binding to subtypes of bone marrow and blood cells was seen for 13 antibodies. For the eight most promising MAbs the binding to ten SCLC cell lines was moderate to strong in 47 MAb/cell line combinations, and low or insignificantly in 33 combinations. Three cell lines lacked antigen for all MAbs studied. Flow cytometry was significantly less sensitive than immunocytochemistry in assessing MAb binding to both normal and tumour cells. The antigen expression was for several MAbs higher in exponentially growing tumour cells than in cells in stationary growth phase. Seven of the MAbs, which originally showed low to moderate cross-reactivity with normal cells, were titrated down to the lowest concentrations at which they stained H-146 tumour cells with high levels of antigen expression. At these concentrations five (MLuC1, Oat-1, SM-1, NCC-Lu-243, LAM2) of the seven Mabs showed acceptably low binding to bone marrow cells. At optimal concentrations altogether four to nine of the 17 antibodies studied may be used to detect tumour cell involvement in bone marrow of SCLC patients.

Antibodies, Monoclonal↗

PubMedDate not supplied

Alternating chemotherapy with cyclophosphamide, doxorubicin, vincristine and cisplatin, etoposide followed by prophylactic cranial and thoracic irradiation for small cell lung cancer (SCLC): long-term results.

Both CAV (Cyclophosphamide, Doxorubicin, Vincristine) and PE (Cisplatin, Etoposide) are effective and non cross-resistant regimens in the treatment of SCLC. We designed a chemotherapeutic scheme including CAV and PE given in an alternating fashion with the following schedule: Cyclophosphamide 1000 mg/sm, Doxorubicin 50 mg/sm, Vincristine 2 mg/sm I.V. on day 1, alternated every 21 days with Cisplatin 20 mg/sm and Etoposide 80 mg/sm I.V. days 1-5 for 6 cycles. Following chemotherapy (CT) chest radiotherapy in patients (pts) with limited disease (LD) in complete response (CR) or partial response (PR) and prophylactic cranial irradiation (PCI) in CRs were given, 32 pts entered the study and 27 were evaluable: 9/27 (33.3%) had CR (8/15 with LD had CR) and 15/27 (55.5%) PR. The overall median survival was 53.71 weeks: 79.85 weeks for LD pts and 32.86 for ED.4 pts with LD were alive after 2 years and 2 of them are still alive without disease at 44 and 46 months. Toxicity was acceptable in all patients. Alternating chemotherapy with CAV and PE followed by chest and brain RT in responding LD pts is an effective induction treatment for SCLC although long-term survival still remains disappointing.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Predictive and prognostic factors in small cell lung carcinoma (SCLC)--analysis from routine clinical practice.

BACKGROUND: Prognostic and predictive factors of routine clinical practice among patients with small cell lung carcinoma (SCLC) were evaluated. PATIENTS AND METHODS: Data from 106 patients with SCLC treated by first-line adriamycin, cyclophosphamide and etoposide (ACE) chemotherapy were analyzed. Multivariate analysis was performed. RESULTS: The median overall survival (mOS) of patients was 9.36 months with mOS of 31%, 8% and 3% after 1, 2 and 5 years, respectively. Using multivariate analysis ECOG performance status (p =0.008) and white blood count (WBC) (p=0.022) were independent prognostic factors for mOS. With both, three groups of outcome (good, intermediate, poor) resulting in mOS of 15.8 months, 6.87 months and 3.35 months (p<0.0001) could be established, respectively. The absence of brain metastases (p=0.002), dose reduction (p=0.002) and LDH value (p=0.017) were independent predictive markers. Additionally, female gender was predictive (p=0.025) for complete response (CR). CONCLUSION: Patients with a poor prediction profil might not benefit from ACE chemotherapy. As a consequence, prognostic/predictive factors should be included as stratification criteria in prospective clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Lack of correlation between levels of MHC class I antigen and susceptibility to lysis of small cellular lung carcinoma (SCLC) by natural killer cells.

Small cellular lung carcinoma (SCLC) cell lines are susceptible to lysis by NK cells. SCLC, normally negative for MHC class I Ag, were rendered positive for HLA-A and -B Ag by two methods: treatment with IFN-gamma or transfection with HLA class I genes. Exposure to IFN-gamma induced high levels of class I Ag and reduced susceptibility to NK-mediated lysis. However, transfection with either HLA-A2, HLA-B27, or HLA-B27 with beta 2m did not result in reduced susceptibility to NK cells. These transfectants expressed amounts of HLA class I Ag comparable to those in IFN-gamma-treated, untransfected cells. Transfection with the beta 2m gene or plasmid alone neither influenced levels of surface class I Ag nor resulted in reduced susceptibility to lysis by NK cells. Thus, the effects of IFN-gamma on NK susceptibility can be dissociated from the induction of class I Ag.

Carcinoma, Small Cell↗

PubMed1989

[Pilot phase II study of hybrid chemotherapy of CAV-PVP in small cell lung cancer (SCLC)].

A pilot phase II study of a hybrid chemotherapy for SCLC has been conducted between October 1986 and March 1988. Dose and schedule of the regimen were as follows: CTX, 700 mg/m2, on day 1; ADM 30 mg/m2, on day 1; VCR, 1.4 mg/m2, on day 1 (CAV); and CDDP, 60 mg/m2, on day 8; VP-16, 100 mg/m2, on days 8 and 9 (PVP). Courses were repeated q. 4 weeks up to 6 cycles. Patients with LD received chest irradiation at a dose of 50 Gy when maximal response was achieved. Thirty-six patients were fully evaluated for tumor response and toxicity. All 18 patients with LD responded to the regimen including 11 CRs (61%); there were 7 CRs (39%) and 9 PRs (50%) in patients with ED. Fourteen of the 18 patients with LD have survived for 7 to 22 months, against 12.8 months in ED patients. The major toxicity was myelosuppression, but it was well tolerated. These results indicate that hybrid chemotherapy is highly effective for SCLC, and warrants further clinical trials.

Aged↗

PubMed1987

[G-banded chromosome analysis of bone marrow and peripheral blood cells from small cell lung cancer (SCLC) patients].

Detailed G-banded chromosome analysis was carried out on the bone marrow and/or PHA-stimulated peripheral blood cells from 17 SCLC patients (14 males and 3 females), who were diagnosed cytologically or pathologically or both. Twelve of them had no prior treatment and 16 had a heavy smoking history. High chromosome aberration rates were found in the bone marrow (31% for average structural aberration rate and 63% for numerical aberration rate) and peripheral blood cells (37% for average structural aberration rate and 49% for numerical aberration rate). The smoking index, as a whole, was positively correlated to the structural chromosome aberration rate, indicating that smoking is one of the most important environmental factors in causing chromosome aberrations. But some patients gave a high aberration rate dis-proportional to their smoking index, suggesting that genetically determined susceptibility to smoking or even other factors also play an important role. The structural chromosome aberrations in the bone marrow and peripheral blood cells were mainly clustered on chromosome 3 and chromosomes 1, 9 and 11, respectively. The aberration types were manifold and complicated. No consistent or specific aberration as del 3p14-23 for SCLC was found in this study.

Bone Marrow↗

PubMed1984

[Randomized systemic chemotherapy using two or three drug combination for small cell lung cancer (SCLC)].

Randomized trials were sequentially performed in SCLC patients using a two-drug combination (ACNU . VCR, ADM . VCR) and a three-drug combination (ACNU . CPA . VCR, ACNU . ADM . VCR). The response rate for the two-drug regimen was 36.4% (8/22 cases) and that for the three-drug combination was 60.0% (15/25 cases). The median survival time of the two groups was 7 and 9 months, respectively. The group with PS. 0-1 showed a better prognosis than that with PS. 2-3 (p = 0.03). No fatal side effects were experienced in this protocol. These data suggest that the three-drug combination (ACNU . VCR . CPA) represents an active regimen for SCLC.

Adult↗

PubMed1994

[The combined treatment with surgery and chemotherapy: primary approach to small cell lung carcinoma (SCLC)].

Forty cases of small cell lung carcinoma (SCLC) treated with surgical and chemotherapeutic combined therapy were reported. There were 28 males and 12 females in the group, most with history of more than 2 months, ranging in age of 27-66 years old. Cough, bloody sputum, low fever and chest distress are the main clinical manifestation. The small cell undifferentiated carcinoma was confirmed by fiberbronchoscope examination and pathology in all patients. Single lobectomy was performed in 20 cases, lobectomy of the upper and middle lobe in 9 cases, (sleeve resection of the lobarbronchus in 3 cases), and total pneumonectomy in 7 cases. Two cases were of stage I, 18 were of stage II, and 20 were of stage IIIa. Twelve patients received chemotherapy after operation, and 28 patients underwent the "chemotherapy-operation-chemotherapy" treatment model. Adriamycin (or CDDP), cytoxan, vincristin, and dexomathasone were used for the chemotherapy procedure. The 1, 3, 5-year survival rate of chemotherapy after operation and chemotherapy-operation-chemotherapy group were 70%, 45%, 30.5% and 54%, 30% and 22%, respectively. It is demonstrated that the long-term survival rate could be elevated in SCLC patients treated with chemotherapy after surgical operation, and the chance of operation also could be elevated by preoperative chemotherapy. The resection rate was 93% in the preoperative chemotherapy group.

Adult↗

PubMed1993

[CAV-PVP chemotherapy and sequential thoracic irradiation (TI) for patients with limited (LD) small cell lung cancer (SCLC)].

In order to assess the effectiveness of sequential TI for the treatment of LD SCLC, we analyzed 69 patients who had received CAV-PVP chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, cisplatin and etoposide, plus sequential TI between 1986 and 1992. TI was delivered at a total dose of 50 Gy, 5 fractions/week for 5 weeks, once patients achieved a maximal response to chemotherapy. Responding patients also received PCI at a total dose of 30 Gy, 5 fractions/week for 3 weeks. Thirty patients achieved CR by chemotherapy and an additional 10 achieved CR after TI, resulting in a CR rate of 58.0%. Of 40 patients achieving CR, 24 have relapsed so far; the primary (in 15) and the brain (in 4) were the major sites of relapse despite TI and PCI. The median survival time was 18.4 months, with a 2-year survival rate of 39% and 3-year survival rate of 20%. Almost all the patients encountered grade 3 or grade 4 leukopenia while receiving chemotherapy, but the toxicity of TI was generally mild. This treatment is useful for patients with LD SCLC.

Adult↗

PubMedDate not supplied

Do Italian small cell lung cancer (SCLC) specialists share a common language? An analysis based on 549 questionnaires.

Different specialists are involved in the treatment of SCLC: medical oncologists, pneumologists, radiotherapists, and thoracic surgeons; only in large institutions the therapeutic policy is the result of a multidisciplinary approach. In order to investigate the opinions of the Italian physicians about the state of the art in the diagnosis and treatment of SCLC, 2369 questionnaires have been sent to an equal number of specialists. Each questionnaire contained 16 topics addressing what we consider major open questions. The analysis is based on 549 interpretable questionnaires received back (23.1%). The general attitude of responding physicians is quite pessimistic on the present state of the art; the large majority considering insufficient the current knowledge of both clinical and basic research. Some differences have been registered, among different specialists, regarding the role of surgery and radiation therapy in prolonging the expected survival; while a nearly unanimous consensus has been reached on the role of radiation therapy for local control. Optimism merges about the possibilities of ameliorating the survival in the next decades: 48% have confidence in new drugs, 45% in the development of integrated modalities, and 41% in the application of basic research.

Adult↗

PubMedDate not supplied

Surgery in SCLC as first step of multimodality treatment.

186 patients received surgery for cure followed by aggressive randomized chemotherapy and PCI. After a median follow-up time of about 60 months the observed 4-year overall survival rate for patients completely resected was: 58% for 68 patients with pT1-3N0M0, and 33% for 27 patients with pT1-3 pN2M0 stages of SCLC. These promising results have to be confirmed by larger cooperative studies to support the recommendation to initiate surgery without delay, i.e. without preoperative chemotherapy for SCLC as well as for the non-SCLCs. From 148 patients in ISC study III after preoperative (neoadjuvant) chemotherapy only 12 received surgery for pT1-3N2M0 but only one of them survived 36 months and none 48 months p.o.

Carcinoma, Small Cell↗

PubMed1993

The role of radiotherapy in the management of small cell lung cancer (SCLC).

In the past decade the management of small cell lung cancer (SCLC) has undergone substantial changes with respect to surgery, chemo- und radiotherapy. Due to combined chemotherapy regimens survival rates increased and the role of radiotherapy has been reevaluated. Despite this, the majority of patients treated with chemotherapy alone failed at the primary site. Several randomized studies have shown that irradiation (35 to 40 Gy) following chemotherapy has increased locoregional control rates. There is no uniform opinion about the treatment volume, fractionation schedule or optimal dose of radiotherapy. Recent reports have demonstrated better local control rates with radiation doses in excess of 45 Gy. Prophylactic cranial irradiation with 20 to 40 Gy is widely used in patients with SCLC and generally accepted in patients with complete remission after chemotherapy. Randomized studies have proven that prophylactic cranial irradiation reduces central nervous system relapses, however, no author has reported so far a significant improvement in survival.

Brain Neoplasms↗

PubMedDate not supplied

Factors influencing response to second-line treatment with teniposide (VM26) in patients with progressive small cell lung cancer (SCLC).

Twenty-eight patients with small cell lung cancer (SCLC), 12 with limited (LD) and 16 with extensive (ED) disease, 22 of them relapsed to first-line treatment and 6 not responsive, were treated with a single-agent second-line treatment consisting of teniposide (VM26) 60 mg/m2, i.v. on days 1 to 5, every three weeks, until progression. After a minimum of two courses, we observed no complete response, 7 (LD/ED = 4/3) partial responses (25%), 4 (LD/ED = 2/2) minor responses (14%), and 17 (LD/ED = 6/11) with no change (61%). Median duration of response (partial plus minor) was 3.5 months (range 1-8). Median duration of survival, from VM26 administration, was in LD 6 months (range 2.5-11), in ED 3 months (range 1.5-6) and in all patients 4 months (1.5-11). Correlating the 11 responses with major prognostic variables present in the patients, we observed that KPS > 70, few initial courses of PL/VP16 and response to first-line treatment were significant determinants for successful salvage treatment. This study suggests the need to consider detailed patient characteristics of exposure to previous treatment before prompting new drug phase II studies on SCLC.

Aged↗

PubMed1994

Low-dose chemotherapy delays relapse of a dominated and resistant sub-population in a heterogeneous human SCLC xenograft in nude mice.

We investigated the influence of cellular heterogeneity on the response to low-dose BCNU chemotherapy of an artificially mixed human small-cell lung cancer (SCLC) xenograft in nude mice containing a BCNU-sensitive and dominating sub-population and a BCNU-resistant and undetectable (dominated) sub-population. The cell lines differed in DNA content, making them distinguishable by DNA flow cytometry (FCM). After 3 weeks of tumor growth, the mice were stratified according to tumor size and randomized to 2 different low-dose treatments with BCNU or no treatment. After a further 3 to 4 weeks, a high-dose treatment (LD10) was given to both groups of treated tumors. Changes in the relative proportions of and cell lines in the tumors were measured by FCM on fine-needle tumor aspirates. At the time of low-dose treatment, all the tumors were totally dominated by the sensitive cells. A temporary response was seen after low-dose treatment. After the high-dose treatment, a similar short response was seen. In the non-treated group, the sensitive cells continued to dominate. At the time of tumor regrowth after the low-dose treatment, most of the tumors continued to be dominated by the sensitive population. At the time of progression after the response to the high-dose treatment, the resistant cell line was the predominant population. If compared with a single high-dose BCNU treatment, the response of tumors treated with a low dose was superior, indicating that the presence of a dominating and slower growing sub-population influenced the outcome of the treatment.

Animals↗

PubMed1995

MRP gene overexpression in a human doxorubicin-resistant SCLC cell line: alterations in cellular pharmacokinetics and in pattern of cross-resistance.

The development of non-P-glycoprotein-mediated multi-drug resistance is a frequent event among lung-cancer cell lines. In an attempt to understand the underlying mechanisms of this phenotype, we have selected a multi-drug-resistant subline (POGB/DX) in vitro for doxorubicin resistance. The original cell line (POGB) was established in vitro from a non-treated patient with a small-cell lung cancer. POGB/DX cells were cross-resistant to other drugs, associated with MDR phenotype. In contrast, they were not resistant to taxol, camptothecin or melphalan, but were instead hypersensitive to 5-fluorouracil. Although expression of the mdr-1 gene was not detected in POGB/DX cells, cellular pharmacokinetics showed a reduced drug accumulation and altered intracellular localization in the POGB/DX cell line. This defect in drug accumulation was associated with overexpression and amplification of the MRP gene. Interestingly, verapamil, a known modulator of P-glycoprotein function, was able to reverse drug resistance and to increase drug accumulation. In Northern-blot analysis no differences in expression of topoisomerase I and II (alpha and beta), DNA polymerase beta, or HSP70 and HSP60 genes were observed between POGB and POGB/DX. Coupled to lack of changes in expression of known resistance factors, overexpression of MRP and modulation by verapamil strongly support a role for this gene product in the development of drug resistance in this SCLC cell system. This study provides evidence that (a) altered cellular pharmacokinetics is related to MRP expression; (b) MRP-mediated phenotype is characterized by a specific pattern of cross-resistance, which does not involve taxol; and (c) verapamil may be effective in modulating the function of the MRP gene product.

Carcinoma, Small Cell↗

PubMed1991

A fusion protein formed by L-myc and a novel gene in SCLC.

Oncogenic activation of myc genes in human cancer involves deregulated expression of myc proteins with no major structural alterations. Here two independent small cell lung carcinoma (SCLC) cell lines were found to express similar novel proteins antigenically related to L-myc. cDNAs corresponding to these proteins were cloned and shown to encode chimeric polypeptides with amino-terminal sequences from a novel gene named rlf joined to the L-myc protein. Although the chimeric mRNAs were shown to be identical, they result from distinct DNA rearrangements. The L-myc fusion protein may represent another activation mechanism of the myc proto-oncogenes.

Amino Acid Sequence↗