scholarly journals Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1412-1417 ◽  
Author(s):  
MJ Ratain ◽  
LS Kaminer ◽  
JD Bitran ◽  
RA Larson ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
De Novo ◽  
Cumulative Risk ◽  
Late Complications ◽  
Small Cell ◽  
First Year ◽  
Acute Nonlymphocytic Leukemia ◽  
Acute Monoblastic Leukemia ◽  
High Doses

Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.

Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1412-1417 ◽  
Author(s):  
MJ Ratain ◽  
LS Kaminer ◽  
JD Bitran ◽  
RA Larson ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
De Novo ◽  
Cumulative Risk ◽  
Late Complications ◽  
Small Cell ◽  
First Year ◽  
Acute Nonlymphocytic Leukemia ◽  
Acute Monoblastic Leukemia ◽  
High Doses

Abstract Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.

scholarly journals Acute nonlymphocytic leukemia, preleukemia, and solid tumors following intensive chemotherapy of small cell carcinoma of the lung

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1393-1397 ◽  
Author(s):  
J Pedersen-Bjergaard ◽  
K Osterlind ◽  
M Hansen ◽  
P Philip ◽  
AG Pedersen ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Solid Tumors ◽  
Small Cell Carcinoma ◽  
Bone Marrow Cells ◽  
Cumulative Risk ◽  
Small Cell ◽  
Acute Nonlymphocytic Leukemia ◽  
Kaplan Meier ◽  
Future Therapy ◽  
Very High

Abstract Six of 796 patients treated with intensive combination chemotherapy for small cell carcinoma of the lung developed overt acute nonlymphocytic leukemia (ANLL) (three patients) or preleukemia with severe refractory cytopenia and clonal cytogenetic abnormalities in bone marrow cells (three patients). The latent period to development of preleukemia or leukemia was less than two years in four of the six patients. The cumulative risk of preleukemia and leukemia according to a Kaplan-Meier estimate was 14.0% +/- 6.9% (mean +/- SE) four years after the start of treatment. The relative risk of overt ANLL was 77, since three cases were observed v 0.039 cases expected, based on the age- and sex- specific incidence of acute nonlymphocytic leukemia in the general Danish population. The risk of secondary solid tumors was not increased. The possible causes of the exceptionally early appearance and very high cumulative risk of leukemic complications found in the present study, as compared to previous experience in other malignant diseases, is discussed, including the implications for future therapy of patients with small cell lung cancer.

Meta-Analysis of Randomized Clinical Trials Comparing Cisplatin to Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer

2004 ◽  
Vol 22 (19) ◽  
pp. 3852-3859 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Keitaro Matsuo ◽  
Hiroshi Ueoka ◽  
Katsuyuki Kiura ◽  
Masahiro Tabata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Hazard Ratio ◽  
Survival Advantage ◽  
Small Cell Lung

Purpose It remains undetermined whether cisplatin and carboplatin are equally effective for advanced non–small-cell lung cancer (NSCLC). We therefore did a meta-analysis of trials that compared cisplatin-based chemotherapy with carboplatin-based chemotherapy. Methods We performed a literature search to identify trials that had investigated the substitution of carboplatin for cisplatin in the treatment of advanced NSCLC. We evaluated these trials for inclusion, rated methodologic quality, and abstracted relevant data. Results Of 1,191 reports, eight trials (2,948 patients) were identified, five of which investigated drug regimens containing platinum plus a new agent. Cisplatin-based chemotherapy produced a higher response rate, but the survival advantage was not significant (hazard ratio = 1.050; 95% CI, 0.907 to 1.216; P = .515). Subgroup analysis revealed that combination chemotherapy consisting of cisplatin plus a new agent yields 11% longer survival than carboplatin plus the same new agent (hazard ratio = 1.106; 95% CI, 1.005 to 1.218; P = .039). Patients on cisplatin-based chemotherapy frequently developed nausea and vomiting; thrombocytopenia was more frequent during carboplatin-based chemotherapy. No significant difference in treatment-related mortality was observed. Conclusion We found that combination chemotherapy consisting of cisplatin plus a new agent yields a substantial survival advantage compared with carboplatin plus a new agent in patients with advanced NSCLC, although we failed to find any survival difference in an analysis that included both new and old agents. The strength of our conclusion is limited because we used abstracted data, and careful interpretation is thus required. Nevertheless, our results raise a critical point that needs to be evaluated in future studies.

scholarly journals Acute nonlymphocytic leukemia, preleukemia, and solid tumors following intensive chemotherapy of small cell carcinoma of the lung

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1393-1397
Author(s):  
J Pedersen-Bjergaard ◽  
K Osterlind ◽  
M Hansen ◽  
P Philip ◽  
AG Pedersen ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Solid Tumors ◽  
Small Cell Carcinoma ◽  
Bone Marrow Cells ◽  
Cumulative Risk ◽  
Small Cell ◽  
Acute Nonlymphocytic Leukemia ◽  
Kaplan Meier ◽  
Future Therapy ◽  
Very High

Six of 796 patients treated with intensive combination chemotherapy for small cell carcinoma of the lung developed overt acute nonlymphocytic leukemia (ANLL) (three patients) or preleukemia with severe refractory cytopenia and clonal cytogenetic abnormalities in bone marrow cells (three patients). The latent period to development of preleukemia or leukemia was less than two years in four of the six patients. The cumulative risk of preleukemia and leukemia according to a Kaplan-Meier estimate was 14.0% +/- 6.9% (mean +/- SE) four years after the start of treatment. The relative risk of overt ANLL was 77, since three cases were observed v 0.039 cases expected, based on the age- and sex- specific incidence of acute nonlymphocytic leukemia in the general Danish population. The risk of secondary solid tumors was not increased. The possible causes of the exceptionally early appearance and very high cumulative risk of leukemic complications found in the present study, as compared to previous experience in other malignant diseases, is discussed, including the implications for future therapy of patients with small cell lung cancer.

Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7.

1986 ◽  
Vol 4 (3) ◽  
pp. 325-345 ◽  
Author(s):  
M M Le Beau ◽  
K S Albain ◽  
R A Larson ◽  
J W Vardiman ◽  
E M Davis ◽  
...  
Keyword(s):  
Blood Cells ◽  
Alkylating Agent ◽  
Chromosome Region ◽  
Late Complications ◽  
Cytotoxic Chemotherapy ◽  
Acute Nonlymphocytic Leukemia ◽  
Primary Disorder ◽  
High Doses ◽  
Cytotoxic Therapies ◽  
Previous Disease

Clinical, histologic, and cytogenetic features in 63 patients with a therapy-related myelodysplastic syndrome (t-MDS) or acute nonlymphocytic leukemia (t-ANLL) following cytotoxic chemotherapy or radiotherapy for a previous disease were analyzed. Eleven patients had received only radiotherapy for the primary disorder. In most cases, high doses had been administered to treatment ports that included the pelvic or spinal bone marrow. Twenty-one patients had received only chemotherapy for their primary disease, all for more than 1 year and all but one with an alkylating agent, either alone or in combination with other drugs. Thirty-one patients had received both radiotherapy and chemotherapy, either concurrently or sequentially. A clonal chromosomal abnormality was observed in marrow or blood cells from 61 of the 63 patients (97%). Fifty-five patients (87%) had a clonal abnormality of chromosomes no. 5 and/or 7 consisting of loss of all or part of the long arm of the chromosome. The critical chromosome region that was consistently deleted in all 17 patients with del(5q) comprised bands q23 to q32. In addition to nos. 5 and 7, five other chromosomes (no. 1, 4, 12, 14, and 18) were found to be nonrandomly involved. Both t-MDS and t-ANLL are late complications of cytotoxic therapies that have distinctive clinical and histologic features and are associated with characteristic aberrations of chromosomes no. 5 and 7. It seems likely that these two chromosomes contain genes involved in the pathogenesis of these hematopoietic neoplasms.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

scholarly journals Liquid Biopsy for Small Cell Lung Cancer either De Novo or Transformed: Systematic Review of Different Applications and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2265
Author(s):  
Elio Gregory Pizzutilo ◽  
Martino Pedrani ◽  
Alessio Amatu ◽  
Lorenzo Ruggieri ◽  
Calogero Lauricella ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
De Novo ◽  
Meta Analysis ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

Combination chemotherapy with cisplatin, vindesine and mitomycin‐C for advanced, inoperable non‐small‐cell lung cancer

1992 ◽  
Vol 156 (10) ◽  
pp. 698-700 ◽  
Author(s):  
Martin Stockler ◽  
Derek Raghavan ◽  
Brian C McCaughan ◽  
John Grygiel ◽  
Edward McNeil ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mitomycin C ◽  
Cell Lung Cancer ◽  
Combination Chemotherapy ◽  
Small Cell ◽  
Small Cell Lung

196 Checkpoint blockade therapy for brain-metastatic non-small cell lung cancer: a comparative effectiveness analysis of national data

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A211-A211
Author(s):  
Nayan Lamba ◽  
Bryan Iorgulescu
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Second Line ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
Survival Analyses ◽  
Stage 4 ◽  
Insured Patients

BackgroundManagement of advanced non-small cell lung carcinoma (NSCLC) has been transformed by PD-1/PD-L1 immune checkpoint inhibitors (ICI), with FDA approvals in 2015 (second-line) and 2016 (first-line). Despite ~40% of NSCLC patients developing brain metastases, these patients were disproportionately excluded from the pioneering ICI trials. Thus herein we evaluate the overall survival (OS) associated with ICI in NSCLC brain metastases nationally.MethodsPatients newly-diagnosed with stage 4 NSCLC, including brain metastases, from 2010–2016 were identified from the National Cancer Database (comprising >70% of all newly-diagnosed cancers in the U.S.) Landmark survival analysis was used to address immortal time bias. Post-approval, median time from diagnosis to ICI was 58 days, and this timepoint was selected for all landmark survival analyses (OS estimated by Kaplan-Meier technique, and compared by logrank test and multivariable Cox regression) and for multivariable logistic regression to identify predictors of ICI utilization.Results50,858 patients presented with advanced NSCLC that involved the brain: representing 27.6% of all newly-diagnosed stage 4 cases. Following initial FDA approvals in 2015, ICI use in brain metastasis patients rose from 7.2% in 2015 to 12.7% in 2016. OS for NSCLC brain metastasis patients diagnosed post-approval (i.e. 2015, median 6.3 months, 95% [confidence interval] CI: 6.0–6.6) was substantially better than those diagnosed pre-approval (median 5.5 months, 95%CI: 5.4–5.7, p<0.001) and, in fact, than those diagnosed in 2014 (median 5.9 months, 95%CI: 5.6–6.1, p=0.002). Among patients diagnosed post-approval (in 2015, n=7,431), ICI receipt demonstrated substantially improved OS in landmark survival analyses (median 13.8 months, 95%CI: 12.2–15.1; vs. 8.5 months, 95%CI: 8.3–8.9, p<0.001) – benefits which persisted in multivariable landmark survival analyses (hazard ratio [HR] 0.83, 95%CI: 0.71–0.96, p=0.02), independent of patient characteristics, other therapies, and extracranial disease. For patients diagnosed post-approval, who reached the landmark timepoint, ICI receipt was independent of patient demographics, socioeconomic status, and hospital type—with the exception of Medicaid-insured patients, who were less likely than privately insured patients to receive ICI (OR 0.77, 95%CI: 0.60–0.97, p=0.03).ConclusionsNationally, the use of ICI for NSCLC brain metastasis patients is increasing, generally without significant socioeconomic barriers. Brain metastasis patients diagnosed in the post-approval second-line ICI era (2015) demonstrated significantly better OS than patients diagnosed pre-approval and even than patients diagnosed only in 2014. ICI was associated with a >60% relative increase in median OS. Together our findings from a real-world population demonstrate that the dramatic OS benefits of ICIs for advanced NSCLC also extended to brain metastasis patients.

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