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 »  Abstract
 » Introduction
 » Material and Methods
 » Results
 » Discussion
 » Conclusion
 » Acknowledgment
 »  References
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  Table of Contents  
SYMPOSIUM FOR METRONOMICS AND ECONOMICS-ORIGINAL ARTICLE
Year : 2013  |  Volume : 50  |  Issue : 2  |  Page : 122-127
 

Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer


Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication27-Aug-2013

Correspondence Address:
K Prabhash
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.117032

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 » Abstract 

Context: There are limited effective therapeutic options in the relapsed setting for non-small cell lung cancer (NSCLC) or in the first line for platinum-ineligible patients. Aim: To evaluate the safety and efficacy of a metronomic schedule of paclitaxel administered weekly in relapsed refractory NSCLC or upfront in patients not eligible for platinum-based chemotherapy. Settings and Design: Retrospective analysis of a prospectively collected database from the medical oncology department at Tata Memorial Hospital in Mumbai, India. Materials and Methods: Patients with recurrent and treatment-naïve platinum-ineligible advanced NSCLC were treated with weekly paclitaxel at 80 mg/m 2 with palliative intent. Restaging scans were obtained every two months. Chemotherapy was continued until progressive disease, intolerable side effects, or decision of the patient. Statistical Analysis Used: SPSS version 16 was used for analysis. Simple percentages were used for descriptive statistics. Progression-free survival (PFS) was calculated from date of start of paclitaxel till the date of progression, change of therapy due to any reason, or death due to any cause. Overall survival (OS) was calculated from date of start of paclitaxel to death. The Kaplan Meier method was used for estimation of survival. Results: There were 37 patients over eight months. The median age was 59 years, with a male-to-female ratio of 5:1. Two patients received paclitaxel in the first line, 18 patients in second line, nine in third line, five in fourth line, and three were in fifth line. 73% patients had received prior platinum and 48.6% patients had Eastern Cooperative Oncology Group performance status (ECOG PS) >2. The median number of weekly cycles delivered was 14. The response rate was 35% [complete remission (CR): 2.7%, partial remission (PR): 32.4%, stable disease (SD): 32.4%, progressive disease (PD): 27%], the median PFS was four months, and the estimated median OS was seven months. Chemotherapy was well tolerated. The most frequent grade 3 toxicities included anemia: 8%, neutropenia: 5.4%, and sensory neuropathy: 8%. There were no grade 4 toxicities and no episodes of febrile neutropenia. Conclusions: Weekly low-dose continuous metronomic-type scheduling of paclitaxel is safe and effective for relapsed refractory NSCLC and in the first line in platinum-ineligible patients.


Keywords: Lung cancer, metronomic, non-small-cell lung carcinoma, refractory, relapsed, second line, non-small cell lung cancer


How to cite this article:
Noronha V, Patil V M, Joshi A, Prabhash K. Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer. Indian J Cancer 2013;50:122-7

How to cite this URL:
Noronha V, Patil V M, Joshi A, Prabhash K. Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer. Indian J Cancer [serial online] 2013 [cited 2019 Oct 13];50:122-7. Available from: http://www.indianjcancer.com/text.asp?2013/50/2/122/117032



 » Introduction Top


Systemic chemotherapy decreases symptoms, prolongs survival, and improves quality of life in advanced metastatic non-small-cell lung cancer (NSCLC). [1],[2] There are numerous chemotherapeutic options; however, in the first-line setting, a platinum-containing doublet is the standard of care. [3] These platinum doublets maybe excessively toxic in elderly patients, patients with compromised performance status, renal dysfunction, or other major comorbidities. [4] In the second-line setting, docetaxel and pemetrexed are the two approved chemotherapeutic agents, with equivalent response rates of 9%, median progression-free survival (PFS) of 2.5 months, and median overall survival (OS) of eight months. [5] The toxicity of docetaxel is substantial and administration in the relapsed setting is challenging. Moreover, with the emergence of data demonstrating a benefit in the use of pemetrexed-based doublets for non-squamous histology in the first line, [6],[7] this option is also closed in the relapsed setting, if it has been used upfront. Epidermal growth factor receptor (EGFR)-targeted oral tyrosine kinase inhibitors (TKI) are another option in the relapsed setting; however, they may not be as effective in patients who are EGFR-negative. [8],[9]

Paclitaxel has been utilized in NSCLC in practically every situation, ranging from adjuvant therapy in early NSCLC to use as a radiosensitizer concurrently with radiotherapy for locally advanced NSCLC to first-line therapy in advanced disease to salvage chemotherapy in the relapsed setting. [10] A variety of dosing schedules have been described including 24-hour infusion, three-hour infusion, and weekly one-hour infusion. [10],[11],[12],[13],[14] The classical dosing and schedule in NSCLC is 175 mg/m 2 to 225 mg/m 2 given as an intravenous infusion over three hours, once every three weeks. [15],[16],[17] In general, in the first-line setting, the response rates described are in the range of 10-38%. The use of weekly schedules has been shown to be associated with significantly less hematological and neurological toxicity. [10] There have been several studies with weekly paclitaxel in the first- and second-line setting reported in the literature. [11],[12],[14],[18],[19],[20],[21],[22],[23],[24],[25] In most of these trials, paclitaxel has been dosed between 80 and 100 mg/m 2 delivered weekly for three weeks, followed by a one-week gap. [11],[20],[23]

Paclitaxel targets the tubulins in a cell, and mediates cytotoxicity by binding to and stabilizing the cellular microtubule assembly, leading to cell cycle arrest in mitosis. [26] The sensitivity of tubulins of different cells in the body is dependent upon the concentration of the drug in the serum. The cytotoxic activity of the drug plateaus at a particular concentration, and further cell kill is attained only by increasing the exposure time to the drug, rather than increasing the dose. [27] Paclitaxel has also been shown to inhibit proliferation of endothelial cells, resulting in antiangiogenic activity, which is independent of its cytotoxic activity. [28] It has been demonstrated from in vitro studies that the vascular endothelium is more sensitive to lower doses of paclitaxel. [29],[30],[31] Thus, metronomic scheduling of paclitaxel, that is, lower doses at more frequent intervals maybe efficacious.

We, therefore, planned a metronomic schedule of paclitaxel at a low dose of 80 mg/m 2 weekly, continuously without a break. We report the preliminary results of this regimen in our population of pretreated patients and in first-line setting in platinum-ineligible patients.


 » Material and Methods Top


This is a retrospective analysis of prospectively collected data of patients with pathologically proven pretreated recurrent and platinum-ineligible advanced NSCLC who were treated with weekly paclitaxel regimen with palliative intent.

Pretreatment evaluation

The patients underwent physical examination and routine hematological and biochemical blood testing prior to chemotherapy. For assessment of the extent of tumor, a contrast enhanced computed tomography of the chest and upper abdomen was obtained. Imaging of other sites [like magnetic resonance imaging (MRI) of the brain, bone scan, etc.] were obtained only if the patient had specific symptoms or there was suspicion of specific metastases on clinical evaluation.

Chemotherapy administration and follow-up

Following standard premedications, paclitaxel was administered at 80 mg/m 2 intravenously over one hour. Chemotherapy was repeated weekly. The patients underwent routine evaluation prior to each cycle. Complete hemogram was checked prior to each cycle and monthly biochemical evaluation was obtained. Dose reduction by 25% was done in patients with life-threatening hematological complications. In patients with adverse events, the next cycle of chemotherapy was postponed until the toxicity had decreased to below grade 3. Assessment of radiological response was done at approximately two-monthly intervals and at symptomatic progression. Chemotherapy was discontinued at the time of progression of disease, intolerable side effects, or decision of the patient. The adverse events during this period were evaluated in accordance with the Common Terminology Criteria for Adverse Events version 4.02 (CTCAE v 4.02). At progression, therapy offered was based on the choice of the physician and the patient. Patients continued to be followed after progression, as per routine standards.

Statistical analysis

SPSS version 16 was utilized for statistical analysis. Descriptive statistics are presented. Only patients who had taken four or more cycles were included in the analysis as it was felt by the authors that this amount of chemotherapy would allow a realistic estimation of the toxicity and effect of therapy. PFS was calculated from date of start of paclitaxel till the date of progression (radiologic PD or subjective deterioration in the absence of objective evidence of PD on scan), change of therapy due to any reason (toxicity, patient request, logistics, etc.) or death due to any cause, whichever occurred earlier. OS was calculated from the date of start of paclitaxel chemotherapy to the date of death from any cause. The Kaplan Meier method was used to estimate survival.


 » Results Top


Demography and details of previous treatment

Between September 2010 and May 2011, 37 patients were included in this analysis. The median age of the patients was 59 years (31-77 years). There was a male preponderance with 31 males (83.8%). The median pack index was 1.5 years (0-125 years). Twenty-four patients had no comorbidities, whereas the remaining 13 had the following: hypertension or diabetes in five patients, both in three, and ischemic heart disease in two. The histology of NSCLC was adenocarcinoma in 25 (73%); the remainder had squamous cell carcinoma. The details of previous treatment are depicted in [Table 1]. The best response to last-received treatment was progressive disease in 23 (62.1%) patients. The median event-free period (EFP) from the last-received treatment was one month.

The performance status was the Eastern Cooperative Oncology Group (ECOG) 1 in 19 patients (51.4%), 2 in seven patients (18.9%), and 3 in 11 (29.7%) patients. The median hemoglobin was 11 mg/dL (8-14.7 mg/dl). The median serum albumin and serum creatinine were 3.8 mg/dL (2.4-4.7 mg/dl) and 1 (0.6 2.10 mg/dL), respectively.
Table 1: Details of previous treatment (TKI)

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Chemotherapy details

A total of 527 cycles was delivered. The median number of cycles delivered was 14 (4-36). Only one patient required reduction of dose due to hematological toxicity. There was a gap in treatment for seven patients. The most common reason for delay in chemotherapy was respiratory infection in four patients; other causes included hematological toxicity in three patients and a logistic reason for one patient. Chemotherapy was discontinued in 30 patients (81.1%). The causes for discontinuation were progressive disease in 17 patients, toxicity in six patients, decision of the patient in six patients, and conversion of unresectable locally advanced disease (post chemoradiotherapy; hence, treated with palliative weekly paclitaxel) in one patient to surgically resectable disease; in this patient, chemotherapy was stopped prior to surgery.

Toxicity

Metronomic weekly paclitaxel was well tolerated. There was no grade 4 toxicity and no episodes of febrile neutropenia. Hospitalization was required for five patients (13.5%), for the management of respiratory infection in three patients and for supportive care in two. The details of other toxicities are shown in [Table 2].
Table 2: Toxicity of metronomic weekly paclitaxel

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Efficacy

The best responses achieved are depicted in [Table 3].
Table 3: Details of response

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The estimated median PFS was four months [Figure 1]. The median overall survival was seven months [Figure 2].
Figure 1: Progression - free survival for patients treated with weekly paclitaxel metronomic chemotherapy for relapsed non-small-cell lung carcinoma

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Figure 2: Overall survival for patients treated with weekly paclitaxel metronomic chemotherapy for relapsed non - small - cell lung carcinoma

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 » Discussion Top


Metronomic chemotherapy may effectively overcome chemoresistance and has the ability to control tumors with minimal side effects. [32],[33],[34],[35],[36],[37],[38] In the palliative setting in NSCLC, our goal is to abrogate symptoms, improve quality of life, and prolong survival. We, therefore, favor a chemotherapy regimen that is simple to administer and has minimal side effects, but is efficacious. In such a scenario, metronomic chemotherapy appears to be an appropriate choice. We used a lower dose, frequent administration of paclitaxel via a weekly schedule to assess if the laboratory-demonstrated antiangiogenic effects translate to real benefits in the clinic.

In the second-line setting in NSCLC, the three approved therapies include pemetrexed, docetaxel, and erlotinib, whereas in the third-line setting, only erlotinib is approved. [3] There is no approved therapy beyond the third-line setting in NSCLC. These therapies, although approved and widely prescribed, have very modest efficacy. The response rates of pemetrexed, docetaxel, and erlotinib in the salvage setting are approximately 9% and median PFS is 2.5 months, and median OS is approximately eight months for chemotherapy and 6.7 months for erlotinib in the second- and third-line setting in EGFR-unselected patients. [5],[8] Toxicity of chemotherapy is not insignificant: Docetaxel leads to 40.2% grade 3/4 neutropenia, 12.7% rate of febrile neutropenia, 19% requirement for growth factor support, and 10.5% requirement for hospitalization to manage drug-related toxicity. Thus, there is tremendous scope for therapies that are less toxic and more effective in the second line and beyond therapy of NSCLC.

We found that metronomic weekly paclitaxel resulted in a response rate of 35%. This has to be viewed in the light of the fact that 46% of patients had received two or more lines of prior therapy. Most of the patients, that is, 27 (72.9%) had prior exposure to platinum. The best response to the last-delivered chemotherapy was PD in 23 patients (62.1%). Thus, our population represented a group of heavily pretreated chemoresistant patients.

Several other authors have reported on the use of weekly taxanes in relapsed NSCLC. The results of these studies are presented in [Table 4]. Thus, our results compare favorably with prior similar studies.
Table 4: Studies that have utilized weekly paclitaxel in NSCLC

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The toxicity of weekly paclitaxel chemotherapy in our patients was minimal. Although 13.5% patients required hospitalization, this was mainly for the management of chest infections and general supportive care. The incidence of hypersensitivity reaction during the administration of chemotherapy was minimal and was seen in only one patient, as a grade 1 reaction. The incidence of grade 3/4 neutropenia was 5.4%, with no episode of febrile neutropenia. The most common grade 3/4 toxicities included anemia and sensory neuropathy in 8%. As expected, symptoms of arthralgia/myalgia were reported by nearly one-fourth of the patients. Other authors have also reported minimal toxicity with the use of weekly paclitaxel in relapsed NSCLC. [Table 5] details ≥grade 3 neutropenia and neuropathy reported in other studies where weekly paclitaxel has been used in the salvage setting in NSCLC.
Table 5: Comparison of toxicity with other studies with similar schedule

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The response rate to weekly paclitaxel chemotherapy ranges from 8 to 38% in various studies [Table 4]. We noted a response rate of 37.5%. Multiple factors have an influence on the response rate and survival in NSCLC, ranging from clinical factors like performance status to molecular factors like EGFR and mutation status of KRAS. Ethnicity may also play some role in the response to chemotherapy, as the response rates noted in some of the Asian studies, specifically the studies reported by Yasuda et al., [20] Juan et al., [21] and Chang et al., [12] were high and comparable to the response rate seen in our patients. The survival noted in our patients, both PFS and OS, are similar to what has been previously reported in the literature. Other authors have reported a PFS between three and five months in the salvage setting for weekly paclitaxel [Table 4]. This is similar or better than the PFS reported for the three Food and Drug Administration (FDA)-approved second-line therapies, although with much less toxicity. Thus, there is a potential to compare weekly paclitaxel metronomic chemotherapy against the standard second- and third-line therapies in NSCLC. Considering our results and the results of studies previously reported, we conclude that weekly paclitaxel is effective and safe in the relapsed setting in NSCLC and in the first line setting in platinum-ineligible patients.


 » Conclusion Top


Weekly low-dose continuous metronomic-type scheduling of paclitaxel is an efficacious regimen with minimal toxicity. This regimen should be compared in future studies to the current second-line standards of single-agent three-weekly docetaxel, pemetrexed, or erlotinib.


 » Acknowledgment Top


We acknowledge the contribution of all the members of the thoracic disease management group (Tata Memorial Hospital, Mumbai) for participating in the care of the patients included in this paper. We acknowledge the support of Dr. Shripad Banavalei head of the department of medical oncology at Tata Memorial Hospital, Mumbai.[40]

 
 » References Top

1.Sculier JP, Moro-Sibilot D. First- and second-line therapy for advanced nonsmall cell lung cancer. Eur Respir J 2009;33:915-30.  Back to cited text no. 1
[PUBMED]    
2.Tassinari D, Scarpi E, Sartori S, Tamburini E, Santelmo C, Tombesi P, et al. Second-Line Treatments in Non-small Cell Lung Cancer. Chest 2009;135:1596-609.  Back to cited text no. 2
[PUBMED]    
3.Azzoli CG, Temin S, Aliff T, Baker S Jr, Brahmer J, Johnson DH, et al. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. J Clin Oncol 2011;29:3825-31.  Back to cited text no. 3
[PUBMED]    
4.Aggarwal C, Langer CJ. Older age, poor performance status and major comorbidities: How to treat high-risk patients with advanced nonsmall cell lung cancer. Curr Opin Oncol 2012;24:130-6.  Back to cited text no. 4
[PUBMED]    
5.Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lungcancer previously treated with chemotherapy. J Clin Oncol 2004;22:1589-97.  Back to cited text no. 5
[PUBMED]    
6.Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543-51.  Back to cited text no. 6
[PUBMED]    
7.Einhorn LH. First-line chemotherapy for non-small-cell lung cancer: Is there a superior regimen based onhistology? J Clin Oncol 2008;26:3485-6.  Back to cited text no. 7
[PUBMED]    
8.Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-32.  Back to cited text no. 8
    
9.Zhu CQ, da Cunha Santos G, Ding K, Sakurada A, Cutz JC, Liu N, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008;26:4268-75.  Back to cited text no. 9
[PUBMED]    
10.Ramalingam S, Belani CP. Paclitaxel for non-small cell lung cancer. Expert Opin Pharmacother 2004;5:1771-80.  Back to cited text no. 10
[PUBMED]    
11.Akerley W, Herndon JE, Egorin MJ, Lyss AP, Kindler HL, Savarese DM, et al. Weekly, high-dose paclitaxel in advanced lung carcinoma: A phase II study with pharmacokinetics by the Cancer and Leukemia Group B. Cancer 2003;97:2480-6.  Back to cited text no. 11
[PUBMED]    
12.Chang AY, Rubins J, Asbury R, Boros L, Hui LF. Weekly paclitaxel in advanced non-small cell lung cancer. Semin Oncol 2001;28:10-3.  Back to cited text no. 12
    
13.Gatzemeier U, Heckmayer M, Neuhauss R, Schlüter I, von Pawel J, Wagner H, et al. Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: A phase II trial. Semin Oncol 1995;22:24-8.  Back to cited text no. 13
    
14.Fidias P, Supko JG, Martins R, Boral A, Carey R, Grossbard M, et al. A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer. Clin Cancer Res 2001;7:3942-9.  Back to cited text no. 14
[PUBMED]    
15.Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8.  Back to cited text no. 15
[PUBMED]    
16.Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542-50.  Back to cited text no. 16
[PUBMED]    
17.Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, et al. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 2000;18:3390-9.  Back to cited text no. 17
[PUBMED]    
18.Socinski MA. Single-agent paclitaxel in the treatment of advanced non-small cell lung cancer. Oncologist 1999;4:408-16.  Back to cited text no. 18
[PUBMED]    
19.Juan O, Albert A, Villarroya T, Sánchez R, Casan R, Caranana V, et al. Weekly paclitaxel for advanced non-small cell lung cancer patients not suitable for platinum-based therapy. Neoplasma 2003;50:204-9.  Back to cited text no. 19
    
20.Yasuda K, Igishi T, Kawasaki Y, Kato K, Matsumoto S, Katayama S, et al. Phase II study of weekly paclitaxel in patients with non-small cell lung cancer who have failed previous treatments. Oncology 2004;66:347-52.  Back to cited text no. 20
[PUBMED]    
21.Juan O, Albert A, Ordoño F, Casany R, Carañana V, Campos JM, et al. Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: A phase II study. Jpn J Clin Oncol 2002;32:449-54.  Back to cited text no. 21
    
22.Buccheri G, Ferrigno D. Second-line weekly paclitaxel in patients with inoperable non-small cell lung cancer who fail combination chemotherapy with cisplatin. Lung Cancer 2004;45:227-36.  Back to cited text no. 22
    
23.Ceresoli GL, Gregorc V, Cordio S, Bencardino KB, Schipani S, Cozzarini C, et al. Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer. Lung Cancer 2004;44:231-9.  Back to cited text no. 23
[PUBMED]    
24.Gasparini G, Meo S, Comella G, Stani SC, Mariani L, Gamucci T, et al. The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for non-small cell lung cancer: A phase II study with biological correlates. Cancer J 2005;11:209-16.  Back to cited text no. 24
[PUBMED]    
25.Socinski MA, Schell MJ, Bakri K, Peterman A, Lee JH, Unger P, et al. Second-line, low-dose, weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line chemotherapy with carboplatin plus paclitaxel. Cancer 2002;95:1265-73.  Back to cited text no. 25
[PUBMED]    
26.Pellegrini F, Budman DR. Review: Tubulin function, action of antitubulin drugs, and new drug development. Cancer Invest 2005;23:264-73.  Back to cited text no. 26
[PUBMED]    
27.Lopes NM, Adams EG, Pitts TW, Bhuyan BK. Cell kill kinetics and cell cycle effects of taxol on human and hamster ovarian cell lines. Cancer Chemother Pharmacol 1993;32:235-42.  Back to cited text no. 27
[PUBMED]    
28.Belotti D, Vergani V, Drudis T, Borsotti P, Pitelli MR, Viale G, et al. The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res 1996;2:1843-9.  Back to cited text no. 28
[PUBMED]    
29.Wang J, Lou P, Lesniewski R, Henkin J. Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly. Anticancer Drugs 2003;14:13-9.  Back to cited text no. 29
[PUBMED]    
30.Pasquier E, Honore S, Pourroy B, Jordan MA, Lehmann M, Briand C, et al. Antiangiogenic concentrations of paclitaxel induce an increase in microtubule dynamics in endothelial cells but not in cancer cells. Cancer Res 2005;65:2433-40.  Back to cited text no. 30
[PUBMED]    
31.Kobayashi M, Oba K, Sakamoto J, Kondo K, Nagata N, Okabayashi T, et al. Pharmacokinetic study of weekly administration dose of paclitaxel in patients with advanced or recurrent gastric cancer in Japan. Gastric Cancer 2007;10:52-7.  Back to cited text no. 31
[PUBMED]    
32.André N, Banavali S, Snihur Y, Pasquier E. Has the time come for metronomics in low-income and middle-income countries? Lancet Oncol 2013;14:e239-48.  Back to cited text no. 32
    
33.Pasquier E, Kavallaris M, Andre N. Metronomic chemotherapy: New rationale for new directions. Nat Rev Clin Oncol 2010;7:455-65.  Back to cited text no. 33
    
34.Noberasco C, Spitaleri G, Mancuso P, Zorzino L, Radice D, Milani A, et al. Safety, Tolerability and Biological Effects of Long-Term Metronomic Administration of Non-Cytotoxic Anti-Angiogenic Agents. Oncology 2009;77:358-65.  Back to cited text no. 34
[PUBMED]    
35.Gasparini G. Metronomic scheduling: The future of chemotherapy? Lancet Oncol 2001;2:733-40.  Back to cited text no. 35
[PUBMED]    
36.Hanahan D, Bergers G, Bergsland E. Less is more, regularly: Metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 2000;105:1045-7.  Back to cited text no. 36
[PUBMED]    
37.Patil V, Noronha V, Krishna V, Joshi A, Prabhash K. Oral metronomic chemotherapy in recurrent, metastatic and locally advanced head and neck cancers. Clin Oncol (R Coll Radiol) 2013;25:388.  Back to cited text no. 37
[PUBMED]    
38.Patil V, Noronha V, D'cruz AK, Banavali SD, Prabhash K. Metronomic chemotherapy in advanced oral cancers. J Cancer Res Ther 2012;8:S106-10.  Back to cited text no. 38
[PUBMED]    
39.Ichikawa M, Suzuki R, Kataoka K, Noda Y, Shindoh J, Matsumoto S, et al. Second-line weekly paclitaxel in resistant or relapsed non-small cell lung cancer treated with docetaxel and carboplatin: A multi-center phase II study. Lung Cancer 2010;69:319-22.  Back to cited text no. 39
    
40.Camps C, Caballero C, Blasco A, Safont MJ, Berrocal A, Garde J, et al. Weekly paclitaxel as second/third-line treatment in advanced non-small cell lung cancer patients: Efficacy and tolerability. Anticancer Res 2005;25:4611-4.  Back to cited text no. 40
[PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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