Cancer Treatment Today » Small Cell Lung Cancer

Irinotecan for brain metastases of breast and lung cancer -pro

M Levin, MD — Fri, 09 Nov 2012 15:34:51 +0000

Because irinotecan penetrates the brain-blood barrier and has an effect in primary brain cancer, there is some interest in using it for brain metastasis, especially for lung cancer and breast cancer. Most studies of irinotecan had been for brain mets of small(SCLC) and non-small cell lung cancer(NSMCLC) and not breast cancer and have had mixed results. One study reported complete responses with irinotecan-based chemotherapy for brain metastases in three patients with SCLC, parotid cancer, and esophageal adenocarcinoma. The combination of cisplatin, ifosfamide and irinotecan in treatment-naive patients with NSCLC led to an intracranial response rate of 50%. A study of temozolomide (200 mg/m²) on days 1 to 5 and irinotecan (200 mg/m²) on days 1 to 5 every 4 weeks in previously untreated patients with NSCLC brain metastases reported no responses.

There are several ongoing studies for lung cancer. For breast cancer, there is also a study: Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases, NCT00617539.

nccn.org, brain cancers, p.38

Chou R, Chen A, Lau D.Complete response of brain metastases to irinotecan-based chemotherapy.ONCOLOGY. Vol. 22 No. 2

Yun Oh, MD et al, Systemic Therapy for Lung Cancer Brain Metastases: A Rationale for Clinical Trials

J Clin Neurosci. 2005 Apr;12(3):242-5.ONCOLOGY. Vol. 22 No. 2

Chou R, Chen A, Lau D: Complete response of brain metastases to irinotecan-based chemotherapy. J Clin Neurosci 12:242-245, 2005. Fujita A, Fukuoka S, Takabatake H, et al: Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer. Oncology 59:291-295, 2000.For Lay version see here

Amrubicin for small cell lung cancer – pro

M Levin, MD — Thu, 13 Sep 2012 19:02:18 +0000

Amrubicin, previously known as SM-5887, is an anthracycline used in the treatment of lung cancer. It is marketed in Japan since 2002 by Sumitomo Pharmaceuticals under the brand name Calsed. Two phase 2 studies of amrubicin in Japanese populations with previously treated SCLC have shown impressive results. Amrubicin has been granted Fast Track product designation by the U.S. Food and Drug Administration (FDA) for the treatment of small cell lung cancer after first-line chemotherapy.
Amrubicin is being studied in clicnal trials and there are currenlty seven such trials ongoing (http://clinicaltrials.gov/ct2/results?term=amrubicin)

Etoposide and carboplatin for small cell lung cancer – pro

M Levin, MD — Thu, 13 Sep 2012 19:00:07 +0000

Standard treatment for patients with extensive SCLC include VePesid® (etoposide) plus Platinol, VePesid plus Paraplatin or Camptosar® (irinotecan) plus Platinol. Etoposide and carboplatin is standard chemotherapy, which is supported by the NCCN guideline. VePesid (etoposide) Capsules in combination with other approved chemotherapeutic agents is FDA approved as first line treatment in patients with small cell lung cancer. The IV equivalent, Vepesid and ETOPOPHOS (etoposide phosphate) is also FDA approved for Injection in combination with other approved chemotherapeutic agents as first-line treatment in patients with small cell lung cancer.
Although carboplatin is not specifically FDA approved for small cell lung cancer, it certainly qualifies as an approved chemotherapeutic agent under the FDA definition. This combination has been shown to be equivalent to irinotecan and cisplatin and superior to Alimta based regimens in phase 3 comparative trials.

A number of other drugs was studied with etoposide instead of cisplatin but the results are not clearly superior and cisplatin remains the standard of care.

Socinski M, Weissman C, Hart L, et al. Randomized Phase II Trial of Pemetrexed Combined With Either Cisplatin or Carboplatin in Untreated Extensive-Stage Small Cell Lung Cancer. Journal of Clinical Oncology . 2006;2 4:4840-4847.

ee SM, James LE, Qian W, et al. Comparison of gemcitabine and carboplatin versus cisplatin and etoposide for patients with poor-prognosis small cell lung cancer. Thorax 2009; 64:75.

Andreas Hermes, Bengt Bergman, Roy Bremnes, Lars Ek, Sverre Fluge, Christer Sederholm, Stein Sundstrøm, Lars Thaning, Jan Vilsvik, Ulf Aasebø and Sverre Sörenson, Irinotecan Plus Carboplatin Versus Oral Etoposide Plus Carboplatin in Extensive Small-Cell Lung Cancer: A Randomized Phase III Trial JCO September 10, 2008 vol. 26 no. 26 4261-4267

nccn.org, small cell lung cancer, 2018

Niwa H et al, Safety and efficacy of carboplatin plus nab-paclitaxel for treating advanced non-small-cell lung cancer with interstitial lung disease.Mol Clin Oncol. 2017 Oct;7(4):604-608.

PET scan in small cell lung cancer – pro

M Levin, MD — Thu, 13 Sep 2012 13:21:34 +0000

PET with 2-[fluorine 18]-fluoro-2-deoxy-D-glucose (FDG) has recently received attention, and growing evidence suggests its superiority in the staging of lung cancer. However, PET is more frequently used in evaluating patients with NSCLC to identify surgical candidates. It is less commonly used in patients with SCLC because most of these patients are not candidates for surgery. PET may be useful for evaluating cases in which recurrent disease but this is questionable.Generally, the resolution of PET is not considered good for lesions smaller than 1 cm. The PET results can also overlap with the standard uptake values (SUVs) in some benign lesions and malignant lesions.Unfortunately, specificity, sensitivity and accuracy compared to CT are not securely known. The utility of positron emission tomography (PET) scanning in patients with SCLC has been recently reported in two small prospective studies. In a study reported by Hauber et al, PET scans detected all primary lesions, lymph node metastases, and distant metastases that had been detected by other standard staging procedures. In a second study, 30 patients with SCLC were evaluated with 36 PET scan examinations, and the results were compared with the sum of the other staging procedures. The results of 23 of the 36 PET scan examinations were concordant with those of the other staging procedures. In seven cases, the PET scan examination resulted in upward staging of the patient, and in one instance the PET scan revealed the presence of a viable tumor when conventional staging procedures had revealed no residual disease. PET scan identified all areas of tumor involvement detected by other staging procedures. A third study looked at the accuracy of PET scanning in detecting bony metastases in patients with SCLC and NSCLC, comparing the PET scans to bone scans and single-photon emission CT scans. In this study, PET scans were found to be the most accurate whole-body imaging modality for the screening of bone metastases. These and similar studies suggested that PET scanning is likely to be a useful staging tool in patients with SCLC. However, all the studies were small, and the experience with PET scan as a staging tool remains largely limited.

NCCN 2015, SCL – 1 says that PET should be used only if limited disease is suspected. On p. SCL-6 it mentions “other imaging studies” as clinically indicated.

PET scan has not been sufficiently studied for small celll lung cancer to be considered standard and it is not Medicare approved. NCCN mentions PET for initial staging but not for restaging.

P. Chirrmeister, H, Glatting, G, Hetzel, J, et al Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer. J Nucl Med 2001;42,1800-1804

Hauber, HP, Bohuslavizki, KH, Lund, CH, et al Positron emission tomography in the staging of small-cell lung cancer: a preliminary study. Chest 2001;119,950-954

Schumacher, T, Brink, I, Mix, M, et al FDG-PET imaging for the staging and follow-up of small cell lung cancer. Eur J Nucl Med 2001;28,483-48

Seute T, Leffers P, ten Velde GP, Twijnstra A. Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI). Cancer. Apr 15 2008;112(8):1827-34.

Lee HY, Chung JK, Jeong JM, Lee DS, Kim DG, Jung HW, et al. Comparison of FDG-PET findings of brain metastasis from non-small-cell lung cancer and small-cell lung cancer. Ann Nucl Med. May 2008;22(4):281-6.

Delay in diagnosis of lung cancer – pro

M Levin, MD — Mon, 10 Sep 2012 17:47:40 +0000

Lung cancer is symptomatic in over 90% of patients. However, studies find that delays between reporting of symptoms and diagnosis are universal. In a recent Swedish study, 134 lung cancer patients were investigated prospectively. The median delay for the patients, i.e. from the first symptom(s) until the family doctor was contacted, was 21 days. From the first contact with the doctor until referral to the specialist the median time was 33 days. From the first visit to the specialist to diagnosis the median time was 9 days. The median time from first symptom(s) until treatment or the decision not to treat (the sum of all delays) was 189 days, i.e. 6 months. A large epidemiological survey from Poland in 561 lung cancer patients registered from 1995 to 1998, reported that the median delay caused by patients was 46 days. The median delay caused by doctors (time between first visit to the doctor and the date of diagnosis) was 65 days and the median time between diagnosis and therapy was an additional period of 30 days. Delays were significantly different from region to region. A retrospective audit of the time involved in the management of patients with lung cancer referred for consideration of surgery at the Royal Brompton Hospital in London has been previously carried out on 194 patients. The median interval between the onset of symptoms and their first chest radiograph was 39 days, and between the onset of symptoms and referral to a surgeon by a chest physician was 112 days. In conclusion, the2-month delay between the onset of the first symptom andthe first referral to a lung cancer specialist (a time course that includes both patient and family doctor delay) is somewhat longer than the average national delay (whose figure of 50 days also included the specialist delay) and roughly on line or somewhat better than reported internationally.

Detterbeck FC, Jones DR, Kernstine KH, Naunheim KS. Presentations of lung cancer with special treatment considerations. Chest 2003 Jan;123(1 Suppl):244S-58S. [56 references]

G. Buccheri and D. Ferrigno Lung cancer: clinical presentation and specialist referral time Eur Respir J 2004; 24:898-904

Samsa for hyponatremia – pro

M Levin, MD — Mon, 10 Sep 2012 17:11:48 +0000

SAMSCA is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Thiis condtion occurrs with lung cancer and less commonly other cancer or in associaitons with certain chemotherapy drugs that are used to treat cancer, such as cisplatin.

SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. This allows observing for side efects and to titrate to an appropraite dose. The FDA aproved Prescribing information says: “The usual starting dose for SAMSCA is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. ”

Cavalcante JL, Khan S, Gheorghiade M EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan. Expert Review of Cardiovascular Therapy 2008 Nov;6(10):1331-8

Madias NE Effects of tolvaptan, an oral vasopressin V2 receptor antagonist, in hyponatremia. American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 2007 Aug;50(2):184-7

Miyazaki T, Fujiki H, Yamamura Y, Nakamura S, Mori T Tolvaptan, an orally active vasopressin V(2)-receptor antagonist – pharmacology and clinical trials. Cardiovascular Drug Reviews 2007 Spring;25(1):1-13

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C; Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA : the journal of the American Medical Association 2007 Mar 28;297(12):1319-31

Carboplatin with etoposide and Taxol and platin for small cell lung cancer – pro

M Levin, MD — Tue, 04 Sep 2012 20:47:24 +0000

Small cell lung cancer (SCLC) is different and distinct from other lung cancers, called non–small-cell lung cancers (NSCLCs), because SCLC exhibits aggressive behavior, with rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and frequent association with distinct paraneoplastic syndromes.
Patients with disease confined to one hemithorax, with or without mediastinal, contralateral hilar, or ipsilateral supraclavicular or scalene lymph nodes are considered to have limited-stage disease.Management of limited-stage SCLC involves combination chemotherapy, usually with a platinum-containing regimen, and concurrent or subsequent chest radiation therapy. If the patient achieves a complete remission, he or she may be offered prophylactic cranial irradiation. The combination of cisplatin and etoposide (PE) currently is the most widely used regimen in both limited- and extensive-stage SCLC. Phase III studies suggest that irinotecan is as effective as etoposide with cisplatin. Carboplatin is often substituted for cisplatin and this is supported by NCCN.

A phase 2 study found Taxol/carboplatin insufficiently active to warrant comparison to etoposide/cisplatin in phase III trials. NCCN 9SCL-B,1) does not list this regimen. It recommends irinotecan based regimns. NCI (PDQ) recommends: 1.Combination chemotherapy with or without PCI given to patients with complete responses: •EP or EC: etoposide plus cisplatin or carboplatin.Other regimens that appear to produce similar survival outcomes but have been studied less extensively or are in less common use include:

•CAE/CDE: cyclophosphamide plus doxorubicin plus etoposide.
•ICE: ifosfamide plus cisplatin plus etoposide.
•Cisplatin plus irinotecan.
•Cyclophosphamide plus doxorubicin plus etoposide plus vincristine.
•CEV: cyclophosphamide plus etoposide plus vincristine.

Accordingly, I do not conider Taxol/carboplatin to be med. necessary. Taxol is being studied in three drug regimens that include topotecan or irnotecan.

Christopher G. Azzoli, Sherman Baker, Jr., Sarah Temin, William Pao, Timothy Aliff, Julie Brahmer, David H. Johnson, Janessa L. Laskin, Gregory Masters, Daniel Milton, Luke Nordquist, David G. Pfister, Steven Piantadosi, Joan H. Schiller, Reily Smith, Thomas J. Smith, John R. Strawn, David Trent, Giuseppe GiacconeASCO Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small Cell Lung Cancer Focused Update of Recommendation A6 published in Journal of Clinical Oncology, Vol 29, No 28 (October), 2011: 3825-3831. Full Guideline published in Journal of Clinical Oncology, Vol 27, No 36 (December), 2009: 6251-6266

http://www.nccn.org/professionals/physician_gls/PDF/sclc.pdf,

C Gridelli1et al ,Published online 3 January 2001
Carboplatin plus paclitaxel in extensive small cell lung cancer: a multicentre phase 2 studyBritish Journal of Cancer (2001) 84, 38–41

M. Sørensen et al, Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol (2010) 21 (suppl 5): v120-v125. 1

http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional/page6

Tai P, Yu E, Battista J, Van Dyk J: Radiation treatment of lung cancer-patterns of practice in Canada. Radiother Oncol 2004 May; 71(2): 167-74

Takada M, Fukuoka M, Kawahara M, et al: Phase III randomized study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Onclology Group Study 9104. J Clin Oncol 2002; 20: 3054-60

Abraxane and Avastin for lung cancer – pro

M Levin, MD — Mon, 03 Sep 2012 00:22:21 +0000

Lay Summary: One phase II study suggests high response rates for Abraxane and Avastin in nonsmall lung cancer.

The combination of Abraxane (albumin bound paclitaxel) and Paraplatin® (carboplatin) and Avastin (bevacizumab) provides responses or disease stabilization in over 75% of patients with chemotherapy-naïve, advanced non-small cell lung cancer (NSCLC). These results were presented at the 2006 annual Chemotherapy Foundation Symposium.

Abraxane consists of the active ingredient paclitaxel, which is found in Taxol® and its generic equivalents. However, in the formulation of Abraxane, paclitaxel is delivered in a suspension of albumin particles, offering several advantages to Taxol and its generic equivalents, in which polyethoxylated castor oil (Cremophor EL) is used as the solvent for paclitaxel.

Results from previous studies have indicated that single-agent Abraxane is well tolerated and produces significant responses in patients with previously un-treated NSCLC. Researchers continue to evaluate Abraxane in combination with other chemotherapy agents, as well as targeted therapies for the treatment of NSCLC.

Results presented at the Chemotherapy Foundation Symposium were from a phase II open-label clinical trial including 50 chemotherapy-naïve advanced NSCLC patients. Treatment included Abraxane (300 mg/m2) and Paraplatin AUC 6 plus Avastin every 3 weeks. Avastin was not continued beyond 4-6 cycles of chemotherapy.

Confirmed responses were achieved in 26% of patients.
Disease stabilization was achieved in an additional 48% of patients.
Hemoptysis occurred in 6% if patients with 1 fatal event.
The researchers concluded that the treatment combination consisting of Abraxane, Paraplatin and Avastin provides responses or disease stabilization in a vast majority of patients with chemotherapy-naïve, advanced NSCLC. These results provide further evidence that Abraxane in combination with other agents is promising in the treatment of NSCLC.

Abraxane is in phase II studies with carboplatin in lung cancer.

Reynolds C, et al. Nab-Paclitaxel/Carboplatin/Bevacizumab in Advanced Non-Squamous NSCLC. Proceedings of the Chemotherapy Foundation Symposium XXIV. New York, New York. November 12, 2006.

nccn.org, lung cancer

Erbitux for lung cancer – pro

admin — Sun, 02 Sep 2012 00:42:34 +0000

Lay Summary: Erbitux is proving to be an active and important agent for lung cancer.

Erbitux binds specifically to epidermal growth factor receptors on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor and other ligands. It is approved for use in combination with irinotecan to treat patients with EGFR-expressing metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and as a single agent in the patients intolerant to irinotecan-based chemotherapy; aslo approved for head and neck. There is less information on its use in lung cancer.

Two single-arm phase II trials testing cetuximab in combination with a platinum-based doublet in previously untreated patients showed responses in the range of 26% to 29%, with median survival times of 10 to 11 months.

A Phase III study of ERBITUX® (Cetuximab) in combination with platinum-based chemotherapy (vinorelbine plus cisplatin) met its primary endpoint of increasing overall survival compared with chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC). This large, randomized multi-national study, known as FLEX (First-Line Treatment for Patients with Epidermal growth factor inhibitor (EGFR)-EXpressing Advanced NSCLC) was conducted by Merck KGaA, Darmstadt, Germany and enrolled patients with Stage IIIB or Stage IV NSCLC who had not previously received chemotherapy. The results were announced in September on 2007 and published in December.Overall survival was 11.3 months in the cetuximab arm versus 10.1 months in the controls (HR-0.871, P =0.044). One year survival was 47% in the cetuximab arm versus 42% in controls. Prespecified ethnic analyses revealed a more impressive response in 946 Caucasian patients-a 10.5-month median overall survival for cetuximab versus 9.1 months (HR 0.803, P =0.003). Median progression-free survival (which was the prospective endpoint) was not different at 4.8 months in both arms.

This is the relevent summary describes what should be considered medically appropriate use of Erbitux: ” First-line therapy for recurrence or metastasis in combination with vinorelbine and cisplatin for performance status 0-2 patients at least 18 years of age with NSCLC IIIB (pleural effusion)/IV, EGFR expression by immunohistochemistry (at least 1 positive tumor cell), no known brain metastases, and no prior chemotherapy or anti-EGFR therapy. ”

Does this recommendation apply to second line therapy? Abstract of a study presented at the 2003 ASCO annual meeting that found cetuximab in combination is well tolerated and the response rate suggests clinical activity in the second-line settingm and this was with Docetaxel. I do not consdier evidence for second line to be conclusive and more studies need to be done.

Pirker, R et al “FLEX: A randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)” Abstract 3 ASCO 2008

nccn.org, lung cancer

Kvale PA, Selecky PA, Prakash UB, American College of Chest Physicians. Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):368S-403S. [358 references]

Govindan, Ramaswamy
Cetuximab in Advanced Non-Small Cell Lung Cancer
Clin Cancer Res 2004 10: 4241S-4244

Single agent Taxol for relapsed small cell lung cancer – pro

M Levin, MD — Sat, 01 Sep 2012 02:01:58 +0000

Small cell lung cancer that progresses after first line chemotherapy has a poor prognosis. A variety of treatments are available, among them single agent Taxol.The literature contains studies in various schedules, including weekly and dose-dense, as well as various combination therapies. Single agent Taxol is also listed for sequential use by NCCN. However, combination regimesn with Taxol have some phase II data, but are not supported by guidelines, such as NCCN and others.

Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. II study of weekly paclitaxel for relapsed and refractory small cell lung cancer.Anticancer Res. 2006 Jan-Feb;26(1B):777-81.

Graziano SL, Herndon JE 2nd, Socinski MA, Wang X, Watson D, Vokes E, Green MR; Cancer and Leukemia Group B.Phase II trial of weekly dose-dense paclitaxel in extensive-stage small cell lung cancer: cancer and leukemia group B study 39901.Thorac Oncol. 2008 Feb;3(2):158-62.

nccn.org, small cell lung cancer, 2103