A mathematical model of drug resistance applied to treatment for small-cell lung cancer.

A mathematical model has been applied to patients with small-cell lung cancer (SCLC) in order to estimate the proportions of resistant and sensitive tumor at presentation, and the efficacy of the treatment, measured in terms of proportions of tumor killed with each cycle of therapy. The model uses estimates of tumor volume obtained from computed tomographic (CT) scans of the chest before each course of chemotherapy. Application of the model to a trial using single-agent high-dose cyclophosphamide (HDC) showed that HDC killed approximately 94% of the sensitive tumor on each application, but that the proportion of tumor resistant to HDC rose from an average of 1% to an average of 15% after the first cycle, assuming a 30-day tumor doubling time. These estimates proved fairly insensitive to different assumptions about tumor doubling time and inaccuracies in volume measurement and may thus provide a useful additional evaluation technique for some clinical trials.

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Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.10.1613 ◽

1990 ◽

Vol 8 (10) ◽

pp. 1613-1617 ◽

Cited By ~ 144

Author(s):

D H Johnson ◽

F A Greco ◽

J Strupp ◽

K R Hande ◽

J D Hainsworth

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Single Agent ◽

Small Cell ◽

Total Leukocyte Count ◽

High Dose ◽

Oral Etoposide ◽

Small Cell Lung ◽

Median Response

Twenty-two patients with recurrent small-cell lung cancer (SCLC) were treated with single-agent etoposide 50 mg/m2/d by mouth for 21 consecutive days. Eleven patients had received previous chemotherapy with cyclophosphamide, doxorubicin, and vincristine (CAV) or etoposide (CAE) or both (CAVE). Four of the latter patients also received salvage treatment with cisplatin and etoposide (EP). Nine patients had been treated with EP as induction therapy, while two patients had received high-dose cyclophosphamide, etoposide and cisplatin (HDCEP). Altogether, 18 patients had received previous intravenous etoposide. The median time off chemotherapy was 4.5 months (range, 1 to 28.9 months). Ten patients (45.5%; 95% confidence interval [CI], 27% to 65%) achieved a complete or partial response. Responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide. Median response duration was 4 months (range, 1.5 to 9.5 months) and median survival was 3.5+ months (range, 1.0 to 15+ months). Leukocyte and platelet nadirs were 1,800/microL and 160,000/microL, respectively, during cycle 1 of treatment and occurred between days 21 and 28. Overall, total leukocyte count decreased to less than 1,000/microL during 10 of 56 cycles (18%). Five patients required six hospitalizations for neutropenia and fever. There were two toxic deaths due to sepsis. Platelet counts less than 50,000/microL occurred in 14 cycles (25%). Alopecia developed in all patients; gastrointestinal toxicity was uncommon. This schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with SCLC.

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First-line cisplatin-fractionated doublet for unfit patients with advanced/metastatic non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18072 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18072-e18072

Author(s):

Giovanni Mansueto ◽

Filomena Narducci ◽

Silvia Quadrini ◽

Maria Laura Mancini ◽

Isabella Sperduti ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Single Agent ◽

Small Cell ◽

Stage Iiib ◽

High Dose ◽

Small Cell Lung ◽

First Line ◽

Unfit Patients

e18072 Background: standard treatment for unfit patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) is single-agent chemotherapy. Such pts are usually not suitable for cisplatin (CDDP)-based chemotherapy due to poor performance status (PS) and/or significant comorbidity that could enhance toxicity of high-dose CDDP. They also are not able to tolerate hydric load that is recommended for CDDP at high doses. We investigated a schedule of fractionated CDDP as first-line treatment in unfit pts with stage IIIB/IV NSCLC. Methods: 42 consecutive unfit pts with advanced/metastatic NSCLC were treated. They all had ECOG PS 2 and/or significant comorbidity and were not eligible for a standard CDDP-based doublet. Median age was 65,6 years (range 46-77), stage IIIB/IV=15/27 pts. Histology: squamous 62,4%, adenocarcinoma 37,5%, other/NOS 0,1%. All pts received q3w CDDP 35 mg/mq d1-8 plus Gemcitabine 1000 mg/mq d1-8 or Pemetrexed 500 mg/mq d1 according to histology, for a maximum of 6 cycles. Maintenance Pemetrexed was allowed in pts with non-squamous histology. Progression-free survival (PFS), clinical benefit rate (CBR) and toxicity were evaluated. Results: 33 pts are evaluable for efficacy and 35 for toxicity. Mean number of cycles per patient was 5,03 (total 211). Maintenance with q3w Pemetrexed was performed in 10 pts (23,8%)(mean 4,3 cycles per patient). Five pts in response after CDDP received thoracic RT. A partial response was observed in 42,5% of pts and a stable disease in 35,4% of pts, for an overall CBR of 77,9%. Median PFS was 10,1 months (Kaplan-Meier); 31,9% of pts were progression-free at 1 year. Pts with adenocarcinoma had significantly better PFS than those with squamous histology (11 vs 8 months, p=0.03). G3-G4 haematological toxicity: neutropenia 48,4% (3% febrile), thrombocytopenia 27,2% and anaemia 9,0%. A 25% dose reduction was required in 39,3% of patients. One patient died for cardiac failure during treatment. Conclusions: fractionated CDDP seems to be effective in our patients population with advanced NSCLC. Adequate supportive care help to manage severe hematological toxicity. A randomized phase II trial of fractionated CDDP-doublet versus monotherapy has been planned.

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Phase III Comparative Study of High-Dose Cisplatin Versus a Combination of Paclitaxel and Cisplatin in Patients With Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.19.3390 ◽

2000 ◽

Vol 18 (19) ◽

pp. 3390-3399 ◽

Cited By ~ 141

Author(s):

Ulrich Gatzemeier ◽

Joachim von Pawel ◽

Maya Gottfried ◽

G.P. M. ten Velde ◽

Karin Mattson ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Single Agent ◽

Small Cell ◽

Phase Iii ◽

High Dose ◽

Time To Progression ◽

Small Cell Lung ◽

Improvement In Survival

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non–small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m2) or a combination of paclitaxel (175 mg/m2, 3-hour infusion) and cisplatin (80 mg/m2) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P = .028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P = .026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P = .862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

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Solid component tumor doubling time is a prognostic factor in non-small cell lung cancer patients

Journal of Cardiothoracic Surgery ◽

10.1186/s13019-019-0879-x ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 3

Author(s):

Kentaro Miura ◽

Kazutoshi Hamanaka ◽

Tomonobu Koizumi ◽

Satoshi Kawakami ◽

Nobutaka Kobayashi ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Doubling Time ◽

Small Cell ◽

Small Cell Lung ◽

Tumor Doubling Time ◽

Lung Cancer Patients

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Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.7.1037 ◽

1986 ◽

Vol 4 (7) ◽

pp. 1037-1043 ◽

Cited By ~ 84

Author(s):

L H Einhorn ◽

P J Loehrer ◽

S D Williams ◽

S Meyers ◽

T Gabrys ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Mitomycin C ◽

Cell Lung Cancer ◽

Single Agent ◽

Objective Response ◽

Small Cell ◽

Phase Iii ◽

High Dose ◽

Small Cell Lung

In this phase III randomized study, 124 evaluable patients with unresectable non-small-cell lung cancer (NSCLC) were randomized to vindesine v cisplatin (120 mg/m2) plus vindesine v cisplatin (60 mg/m2) plus vindesine plus mitomycin C. The objective response rate for cisplatin and vindesine was 27% v 20% for cisplatin, vindesine, and mitomycin C, and 14% for vindesine alone (P = .25 for cisplatin and vindesine v vindesine). The percentage of patients having stable disease (no progression for a minimum of 3 months) was 20% (cisplatin and vindesine), 27% (cisplatin, vindesine, and mitomycin C), and 26% (vindesine alone), respectively. The median survival time for vindesine was 18 weeks, compared with 26 weeks for cisplatin and vindesine and 17 weeks for cisplatin, vindesine, and mitomycin C. Overall survival was not statistically different for cisplatin plus vindesine v vindesine (P = .65). There was no evidence for improved duration of remission or survival of responders with the cisplatin (120 mg/m2) and vindesine arm. This study failed to demonstrate sufficient therapeutic benefit for cisplatin and vindesine (+/- mitomycin C) compared with single-agent vindesine to justify the increased cost and toxicity of these combination regimens.

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High Dose Vitamin A Compound in Treating Participants With Resectable Non-Small Cell Lung Cancer

Case Medical Research ◽

10.31525/ct1-nct03870529 ◽

2019 ◽

Author(s):

Keyword(s):

Lung Cancer ◽

Vitamin A ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

High Dose ◽

Small Cell Lung ◽

High Dose Vitamin

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Phase II trial of high dose epirubicin and ifosfamide in advanced non small cell lung cancer (NSCLC)

Lung Cancer ◽

10.1016/0169-5002(91)91763-2 ◽

1991 ◽

Vol 7 ◽

pp. 111

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Phase Ii Trial ◽

Small Cell ◽

High Dose ◽

Small Cell Lung

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Randomized Phase II Study of Bevacizumab in Combination With Chemotherapy in Previously Untreated Extensive-Stage Small-Cell Lung Cancer: Results From the SALUTE Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.3423 ◽

2011 ◽

Vol 29 (16) ◽

pp. 2215-2222 ◽

Cited By ~ 113

Author(s):

David R. Spigel ◽

Peter M. Townley ◽

David M. Waterhouse ◽

Liang Fang ◽

Ibrahim Adiguzel ◽

...

Keyword(s):

Lung Cancer ◽

Placebo Group ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Single Agent ◽

Small Cell ◽

Small Cell Lung ◽

Randomized Phase Ii ◽

Extensive Stage

PurposeBecause of promising efficacy signals in single-arm studies, a placebo-controlled, double-blind, randomized phase II trial was designed to assess the efficacy and safety of adding bevacizumab to first-line standard chemotherapy for treatment of extensive-stage small-cell lung cancer (SCLC).Patients and MethodsPatients with SCLC were randomly assigned to receive bevacizumab or placebo, with cisplatin or carboplatin plus etoposide, for four cycles followed by single-agent bevacizumab or placebo until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS).ResultsFifty-two patients were randomly assigned to the bevacizumab group and 50 to the placebo group; 69% versus 66%, respectively, completed four cycles of therapy. Median PFS was higher in the bevacizumab group (5.5 months) than in the placebo group (4.4 months; hazard ratio [HR], 0.53; 95% CI, 0.32 to 0.86). Median overall survival (OS) was similar for both groups (9.4 v 10.9 months for bevacizumab and placebo groups, respectively), with an HR of 1.16 (95% CI, 0.66 to 2.04). Overall response rates were 58% (95% CI, 43% to 71%) for the bevacizumab group and 48% (95% CI, 34% to 62%) for the placebo group. Median duration of response was 4.7 months for the bevacizumab group and 3.2 months for the placebo group. In the bevacizumab and placebo groups, 75% versus 60% of patients, respectively, experienced one or more grade 3 or higher adverse events. No new or unexpected safety signals for bevacizumab were observed.ConclusionThe addition of bevacizumab to cisplatin or carboplatin plus etoposide for treatment of extensive-stage SCLC improved PFS, with an acceptable toxicity profile. However, no improvement in OS was observed.

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