Paclitaxel by 96-hour continuous infusion in combination with cisplatin: a phase I trial in patients with advanced lung cancer.

1997 ◽  
Vol 15 (2) ◽  
pp. 735-743 ◽  
Author(s):  
M S Georgiadis ◽  
B S Schuler ◽  
J E Brown ◽  
L V Kieffer ◽  
S M Steinberg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Continuous Infusion ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Survival Duration ◽  
Small Cell Lung ◽  
Median Survival Duration

PURPOSE To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 96-hour continuous infusion in combination with cisplatin, to determine if the addition of granulocyte colony-stimulating factor (G-CSF) permits significant paclitaxel dose escalation, and to assess the toxicity and preliminary activity of this combination in patients with advanced lung cancer. PATIENTS AND METHODS Fifty patients with untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung cancer (SCLC). Patients received paclitaxel doses of 100 to 180 mg/m2/96 hours and cisplatin doses of 60 to 80 mg/m2 as a single 30-minute bolus injection at the end of the paclitaxel infusion. RESULTS Two of six patients experienced dose-limiting neutropenia at a dose of paclitaxel 140 mg/m2/96 hours and cisplatin 80 mg/m2. With G-CSF support, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m2/96 hours and cisplatin 80 mg/m2. Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thirty-three of 42 patients with NSCLC had measurable disease; the objective response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progression and median survival duration were 5 months and 10 months, respectively. The actuarial 1-year survival rate was 41%. Of eight SCLC patients, four responded to therapy, and the median survival duration for all SCLC patients was 11 months. CONCLUSION The MTD without G-CSF is paclitaxel 120 mg/m2/96 hours and cisplatin 80 mg/m2, and the MTD with G-CSF is paclitaxel 160 mg/m2/96 hours and cisplatin 80 mg/m2. Infusional paclitaxel with cisplatin is well tolerated and active in patients with advanced NSCLC.

Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study.

1997 ◽  
Vol 15 (8) ◽  
pp. 2840-2849 ◽  
Author(s):  
A Gregor ◽  
P Drings ◽  
J Burghouts ◽  
P E Postmus ◽  
D Morgan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Survival Duration ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Who Grade ◽  
Grade 3

PURPOSE To evaluate the effectiveness of alternating or sequential schedules of cyclophosphamide, doxorubicin, and etoposide (CDE) chemotherapy and irradiation in patients with previously untreated small-cell lung cancer (SCLC). MATERIALS AND METHODS A total of 335 eligible patients were randomized between five courses of CDE chemotherapy followed by thoracic irradiation 50 Gy in 20 daily fractions (S) and the same total dose of chemotherapy and irradiation split into four courses of five daily fractions delivered on days 14 to 21 of the second and subsequent chemotherapy courses (A). Patients had a median age of 61 years (range, 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weight loss less than 10%. RESULTS The overall median survival duration was 15 months, with 62% (95% confidence interval [CI], 57% to 67%) 1-year, 25% (95% CI, 20% to 30%) 2-year, and 14% (95% CI, 10% to 18%) 3-year survival rates. There was no significant difference between the arms. The median survival time was 14 months in A and 15 months in S. One-year survival was 60% in A (95% CI, 53% to 67%) and 64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%) and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6% to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 90% of A and 77% of S patients (P < .001) and WHO grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P < .001). Rates of other acute and late toxicities were similar in both arms. Hematologic toxicity compromised treatment dose delivery; less than 50% of A patients received greater than 95% of prescribed chemotherapy and 77% their full radiation course, compared with 60% and 93% for arm S (P < .009). Local relapse was the site of first failure in 60% of all patients and 75% of these suffered an in-field relapse; no difference could be seen between the two arms. CONCLUSION This trial failed to confirm the superiority of an alternating schedule of delivery. For this combination of chemotherapy and irradiation, hematologic toxicity compromised treatment delivery and could have contributed to the overall result. The poor rates of local control are disappointing and require intensification of the radiation therapy strategy.

Phase II study of topotecan in metastatic non-small-cell lung cancer.

1994 ◽  
Vol 12 (2) ◽  
pp. 347-352 ◽  
Author(s):  
T J Lynch ◽  
L Kalish ◽  
G Strauss ◽  
A Elias ◽  
A Skarin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Small Cell ◽  
Survival Duration ◽  
Small Cell Lung ◽  
Clinical Responses

PURPOSE Topotecan is an inhibitor of topoisomerase I that has shown preclinical activity against non-small-cell lung cancer (NSCLC). This phase II study was designed to determine the clinical activity and toxicity spectrum of topotecan in untreated patients with metastatic NSCLC. PATIENTS AND METHODS Twenty previously untreated patients received topotecan every 21 days at the dose of 2 mg/m2/d intravenously (IV) for 5 days for two cycles, at which point response was assessed. Patients with either clinical response or stable disease (SD) received additional cycles of the drug until toxicity developed or disease progression (PRG) occurred. RESULTS This study was designed to enter 30 patients. However, because no clinical responses were seen in the first 20 patients entered onto the study, the early-stopping rule was invoked and patient accrual was halted. Eleven patients (55%) had SD on topotecan, and nine (45%) had PRG. Toxicity included neutropenia and rash. The median survival duration for all patients was 7.6 months. CONCLUSION We observed no objective clinical responses despite producing high-grade neutropenia. Phase II trials of topotecan using different schedules or higher doses supported by growth factors may clarify the role of topotecan in the treatment of NSCLC. The combination of topotecan with cisplatin and topoisomerase II inhibitors such as etoposide should be explored. Finally, the median survival duration of 7.6 months for 20 patients treated with an agent that failed to produce any obvious clinical responses compares favorably to the survival obtained with combinations of existing agents. This supports the further study of novel compounds in this clinical setting.

Circulating tumor cell proportion scoring (CTPS) based PD-L1 assessment and clinical application of circulating tumor cells (CTCs) on stage IV non-small cell lung cancer (NSCLC) through liquid biopsy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15031-e15031
Author(s):  
Mi Young Choi ◽  
Da Hye Moon ◽  
Jong-min Jo ◽  
Hae Ung Lee ◽  
Seri Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
False Positive ◽  
Stage Iv ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Diagnostic Strategy ◽  
Small Cell Lung ◽  
Tissue Biopsy

e15031 Background: Stage IV lung cancer is the most advanced lung cancer state accompanied by metastasized to the area around the lungs or distant major organs. The most common type of lung cancer is non-small cell lung cancer, which is more aggressive and may spread quickly due to organ-specific complex networks such as lymph and major blood vessels. Thus, only precise diagnostic strategy approaches will determine the effectiveness of the actual and successful clinical treatment. Until a recent date, Immunohistochemistry (IHC) for programmed death-ligand 1(PD-L1) test is the only available biomarker test that purpose diagnostics (CDx) and guide the treatment with immune checkpoint inhibitors in NSCLC. Methods: Given that CDx strategy, tissue biopsy has inevitable limitations, including patient risk, repetitive examination, sample preparation, sensitivity, and accuracy. For this reason, our research team contrived the best strategy for biomarker, PD-L1-specific CTCs in stage IV NSCLC group (N = 30) compared to pulmonary inflammatory patient groups (N = 30) CytoGen Smart biopsy platform. Herein, we removed false-positive cells for the first strategy of distinguishing between lymphoid/myeloid cells and the enriched-CTCs. And the second strategic approach is to calculate the pure CTCs (without false-positive cells) and then CTPS) as measured by the PD-L1 expression among pure-CTCs. That application is the percentage of viable CTCs showing partial or complete stained cells at the deducted cut-off value in each fluorescence, respectively. Results: Consequently, we demonstrated over 80% of the concordance rate between VENTANA PD-L1(SP263) and DAKO PD-L1(SP263) assay tested by the PD-L1 expression on stage IV NSCLC in tissue and pure-CTCs based CTPS from the blood. In contrast, pure-CTCs based CTPS in the pulmonary inflammatory group were all negative (recorded as zero). Conclusions: Conclusively, this study implicates that pure-CTCs based CTPS could be deployed for innovative diagnosis strategies as alternatives for tissue biopsy. Our clinical study's data suggested that the possibility for prompt decision for diagnosis and gain powerful insights to guide the personalized treatment in NSCLCs. Clinical trial information: 2020-0553.

Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer.

1997 ◽  
Vol 15 (2) ◽  
pp. 744-749 ◽  
Author(s):  
R P Abratt ◽  
W R Bezwoda ◽  
L Goedhals ◽  
D J Hacking
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
World Health ◽  
Survival Duration ◽  
Small Cell Lung ◽  
Who Grade ◽  
Grade 3 ◽  
Specific Agent

PURPOSE The aim of this study was to examine the efficacy of a regimen of initial gemcitabine followed by cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Fifty-three patients (36 men and 17 women; age range, 35 to 74 years) were enrolled. Patients had bidimensionally measurable disease. Gemcitabine (phase-specific agent) was administered on days 1, 8, and 15 at a dose of 1,000 mg/m2. Cisplatin (cycle-specific agent) was administered on day 15 (100 mg/m2). Chemotherapy was administered in 28-day cycles. RESULTS Of 53 patients enrolled, 50 were assessable for response. The overall response rate was 52%. There were two complete responses (4%) and 24 partial responses (48%). The median survival duration was 13 months and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 13.3% and 7.7% of patients, respectively. Most patients experienced mild nausea and vomiting. Few patients had hair loss and oral toxicity was mild. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. For the first two cycles of chemotherapy, the dose-intensity per infusion was 947 mg/m2 for gemcitabine and 85 mg/m2 for cisplatin. CONCLUSION This regimen of gemcitabine and cisplatin was effective, with high response and survival rates and few dosage modifications during its administration. Prospective randomized studies with other cisplatin-based combination chemotherapy regimens are indicated.

scholarly journals A Rare Case of Diffuse Subependymal Periventricular Metastases from Small Cell Lung Carcinoma

2020 ◽  
Vol 13 (3) ◽  
pp. 1304-1310
Author(s):  
Cong Thao Trinh ◽  
Thanh Tam Thi Nguyen ◽  
Hoang Anh Thi Van ◽  
Van Trung Hoang
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Brain Parenchyma ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Small cell lung cancer, whose essence is neuroendocrine tumors, makes up proximately 14–20% of all lung cancer circumstances. Compared to non-small cell lung cancer, its clinical manifestation seems more positive and has a tendency to disseminate earlier in the process of its natural past. About 10% of patients present with brain metastases at the time of provisional diagnosis and sometimes all along the course of their disease, there will be 40–50% of developed brain metastases in addition. Although metastases in the brain parenchyma are often found in patients with advanced lung cancer, periventricular metastases are rare. We report one case of diffuse subependymal periventricular metastases from small cell carcinoma of the lung.

Management of Pneumonitis and Neuropathy in Patients Receiving PD-1–Based Therapy for Non–Small-Cell Lung Cancer

2020 ◽  
Vol 16 (2_suppl) ◽  
pp. 4s-9s ◽  
Author(s):  
Marianne J. Davies ◽  
Anne C. Chiang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Case Examples ◽  
Improved Outcomes ◽  
Programmed Death

Immunotherapy with programmed cell death-1 (PD-1) receptor and programmed death ligand 1 (PD-L1) inhibitors has improved outcomes for certain patients with advanced lung cancer. As use of these therapies has expanded in first-line settings, in patients with different histologies, and in combinations with chemotherapeutic and targeted agents, more patients with lung cancer may benefit from these therapies. However, with expanded use comes greater potential exposure to the immune-related adverse events (irAEs) associated with these immune checkpoint inhibitors (ICIs). This article uses two case examples to illustrate the presentation, evaluation, and management of pulmonary and neurologic symptoms in two patients receiving PD-1–based therapy for non–small-cell lung cancer. These cases illustrate the challenges associated with recognizing pneumonitis and neuropathy in patients receiving ICIs for lung cancer. Although pneumonitis and neuropathy are relatively rare irAEs, they can have devastating or even fatal outcomes if not promptly recognized and managed appropriately. Specific use of guideline-based, multidisciplinary management is emphasized, as illustrated in the Immuno-Oncology Essentials Care Step Pathways.

Increased therapeutic index of weekly doxorubicin in the therapy of non-small cell lung cancer: a prospective, randomized study.

1984 ◽  
Vol 2 (3) ◽  
pp. 207-214 ◽  
Author(s):  
M Valdivieso ◽  
M A Burgess ◽  
M S Ewer ◽  
B Mackay ◽  
S Wallace ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Randomized Study ◽  
Response Duration ◽  
Therapeutic Index ◽  
Small Cell ◽  
Survival Duration ◽  
Small Cell Lung ◽  
Standard Doxorubicin

One hundred patients with non-small cell lung cancer were entered into a randomized evaluation of two schedules of doxorubicin combined with ftorafur, cyclophosphamide, and cisplatin (FACP). Doxorubicin was given either weekly at 20 mg/m2, or every three weeks (standard) at 60 mg/m2. Fifty-two patients were randomized to the FACP/weekly doxorubicin arm and 48 patients to the FACP/standard doxorubicin arm. The FACP/weekly doxorubicin regimen was associated with higher complete and partial remission rates (31% versus 19%), longer response duration (median, 33 versus 21 weeks), and longer survival duration for responders (median, 58 versus 50 weeks). These differences were not significant. Less neutropenia (p = 0.01) and less infectious morbidity (p = 0.05) were observed in the FACP/weekly doxorubicin arm. Twenty-eight patients underwent 35 endomyocardial biopsies to assess doxorubicin-induced cardiotoxicity. Sixteen biopsies were performed in 12 patients receiving cumulative doxorubicin doses ranging from 250 to 1,190 mg/m2 within the FACP/weekly doxorubicin arm. Nineteen biopsies were performed in 16 patients receiving cumulative doxorubicin doses ranging from 250 to 540 mg/m2 within the FACP/standard doxorubicin regimen. The FACP/weekly doxorubicin regimen was associated with significantly lower cardiotoxicity scores (p = 0.01). This study indicates that weekly administered doxorubicin is as effective and less cardiotoxic than the standard schedule.

High-dose induction chemotherapy with cyclophosphamide, etoposide, and cisplatin for extensive-stage small-cell lung cancer.

1987 ◽  
Vol 5 (5) ◽  
pp. 703-709 ◽  
Author(s):  
D H Johnson ◽  
M J DeLeo ◽  
K R Hande ◽  
S N Wolff ◽  
J D Hainsworth ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Induction Chemotherapy ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
High Dose ◽  
Confidence Limits ◽  
Small Cell Lung ◽  
Extensive Stage

To exploit possible dose-response and combination drug synergism, 20 previously untreated patients with extensive-stage small-cell lung cancer (SCLC) received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg), etoposide (1,200 mg/m2), and cisplatin (120 mg/m2) (HDCEP). HDCEP was followed by four cycles of standard-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV). Response was determined after HDCEP and following CAV. Reevaluation included repeat bronchoscopy and chest computerized tomography (CT), as well as repetition of all initially abnormal studies. All patients were evaluable for response and toxicity. Overall response to HDCEP was 90%, with a complete response (CR) rate of 65% (95% confidence limits, 44% to 86%) and a partial response (PR) rate of 25% (95% confidence limits, 6% to 44%). All patients either maintained or improved their initial response while receiving CAV. Median duration of response was 6 months (range, 2 to 12 months) and median survival was 9.5 + months (range, 2 to 21 + months). All 37 courses of HDCEP were associated with leukopenia (less than 1,000/microL), 92% with thrombocytopenia (less than 20,000/microL), and 84% with fever of greater than 38.5 degrees C. Additional toxicities included bacteremia (24%), nausea and emesis (59%), mucositis (57%), diarrhea (38%), and hemorrhagic cystitis (5%). There were two treatment-related deaths due to infection. A third patient died 4 months after completing HDCEP with pulmonary fibrosis. Although response duration and median survival were not improved, HDCEP produced a high CR rate in ambulatory patients with extensive-stage SCLC.

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