Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Belani, C. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Belani, C. P.
(Chest. 2000;117:144S-151S.)
© 2000 American College of Chest Physicians

Paclitaxel and Docetaxel Combinations in Non-Small Cell Lung Cancer*

Chandra P. Belani, MD

* From the Division of Medical Oncology, Department of Medicine, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pittsburgh, PA.

Correspondence to: Chandra P. Belani, MD, University of Pittsburgh Cancer Institute, 200 Lothrop St, MUH N-725, Pittsburgh, PA 15213; e-mail: belanicp{at}msx.upmc.edu


   Abstract
TOP
 Abstract
Introduction
 Paclitaxel in NSCLC
 Docetaxel in NSCLC
 References
 
Paclitaxel, the first of the taxanes, has exhibited unique and encouraging single-agent activity in the treatment of non-small cell lung cancer (NSCLC). Yet, with single-agent response rates approaching 25%, it was logical to examine the impact of paclitaxel in combination chemotherapy regimens. In trials evaluating the activity of paclitaxel in combination with one of the platinum compounds, cisplatin or carboplatin, response rates have ranged from 35 to > 50% and were significantly better than response rates observed with etoposide/cisplatin, the previous standard regimen for treatment of NSCLC. Docetaxel is a newer taxane that also has exhibited notable single-agent activity and response rates ranging from 20 to 50% when combined with cisplatin. Future research will look to refine the use of taxane combinations in NSCLC and to examine the potential of these unique and promising drugs when combined with newer agents that are active against this disease.

Key Words: carboplatin • cisplatin • docetaxel • non-small cell lung cancer • paclitaxel • taxanes


   Introduction
TOP
 Abstract
 Introduction
Paclitaxel in NSCLC
 Docetaxel in NSCLC
 References
 
In this article, we explore the use of paclitaxel and docetaxel combinations in chemotherapy for patients with non-small cell lung cancer (NSCLC).


   Paclitaxel in NSCLC
TOP
 Abstract
 Introduction
 Paclitaxel in NSCLC
Docetaxel in NSCLC
 References
 
Paclitaxel (Taxol; Bristol-Myers Oncology; Princeton, NJ), the first of the taxanes, is a unique antimicrotubule agent that shifts the equilibrium of the cancer cell toward microtubule assembly and stabilizes tubulin polymer formation. This disrupts the normal dynamic reorganization of the microtubule network, which is essential for vital interphase and mitotic function.1 2 Early studies evaluating a 24-h infusion schedule of paclitaxel in the treatment of advanced and metastatic NSCLC (Table 1 ) yielded response rates of 21%3 and 24%.4 The most significant finding from the early trials with paclitaxel was the markedly improved 1-year survival rate, which reached 40%. Subsequent studies using shorter infusion schedules (3-h and 1-h)5 6 7 8 yielded similar results (Table 1) , with the added benefit of the potential for outpatient administration. More recently, dose-dense schedules (full doses administered weekly) (Table 1) also have yielded promising early results in NSCLC patients (response rate, 56%; 1-year survival rate, 53%), although neuropathy and myelosuppression are dose-limiting. The question of whether weekly paclitaxel at maximum dose intensity is, in fact, more effective than the conventional every 3- or 4-week schedule in NSCLC has not yet been answered.


View this table:
[in this window]
[in a new window]

  		Table 1. Paclitaxel: Single-Agent Activity in Advanced NSCLC

 
Paclitaxel Combinations in NSCLC
The provocative results obtained with single-agent paclitaxel prompted its use in combinations with other agents that are active against NSCLC, such as the platinum compounds cisplatin and carboplatin. The combination of paclitaxel with cisplatin produced response rates of 35 to 47% in early phase I/II studies (Table 2 ),11 12 13 although there appeared to be a sequence-dependent increase in myelotoxicity when paclitaxel was administered after cisplatin.14 15 In a large randomized study, the paclitaxel (moderate- and high-dose)/cisplatin combination was compared with a cisplatin/etoposide regimen for the treatment of advanced and metastatic NSCLC (Table 3 ).16 The response rates noted with both paclitaxel doses (moderate-dose regimen, 27%; high-dose regimen, 32%) were significantly higher than those observed with the etoposide/cisplatin regimen (12%); in addition, there was an overall improvement in survival with the paclitaxel-containing arms, which was greatest for patients with stage IIIB disease. These results led to the assignment of paclitaxel/cisplatin rather than cisplatin/etoposide as the reference regimen for the present randomized Eastern Cooperative Oncology Group (ECOG) study (Fig 1 ).17 18


View this table:
[in this window]
[in a new window]

  		Table 2. Paclitaxel (3-h Infusion) and Cisplatin in NSCLC: Phase I/II Studies*

 

View this table:
[in this window]
[in a new window]

  		Table 3. ECOG Phase III Randomized Trial*

 


View larger version (31K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Randomized four-arm ECOG study in patients with advanced and metastatic NSCLC: study design.

 
Carboplatin has comparable activity but a better toxicity profile than cisplatin in patients with NSCLC.19 20 21 22 23 24 As carboplatin is primarily excreted by the kidney, the dose can be individualized based on creatinine clearance or glomerular filtration rates, thus avoiding any undue toxicity and optimizing the therapeutic index. Carboplatin has been evaluated in combination with paclitaxel in a number of phase I/II studies involving patients with advanced and metastatic NSCLC (Table 4 ).25 26 27


View this table:
[in this window]
[in a new window]

  		Table 4. Paclitaxel (24-h Infusion) and Carboplatin in Advanced and Metastatic NSCLC: Phase I/II Studies*

 
Initial studies of the carboplatin/paclitaxel combination using a 24-h infusion of paclitaxel established that myelosuppression was the dose-limiting toxicity.28 29 30 31 In other studies, a shorter 1- or 3-h infusion schedule was associated with a significant decrease in myelosuppression, making neuropathy the dose-limiting toxicity.32 33 34 35 36 37 38 39 40 The various infusion schedules, however, did not diminish the activity observed with paclitaxel/carboplatin in patients with NSCLC (Table 5 and Table 6 ).


View this table:
[in this window]
[in a new window]

  		Table 5. Paclitaxel (3-h Infusion) and Carboplatin in Advanced and Metastatic NSCLC: Phase I–II Studies

 

View this table:
[in this window]
[in a new window]

  		Table 6. Paclitaxel (1-h Infusion) and Carboplatin in Advanced and Metastatic NSCLC: Phase I/II Studies

 
Two unique observations were made from these phase I/II studies of the paclitaxel/carboplatin combination. First, most responses in patients with NSCLC occurred at paclitaxel doses > 175 mg/m2, suggesting a dose-response effect.32 35 Second, the combination was not associated with significant platelet toxicity, suggesting that paclitaxel may exert a myeloprotective effect against thrombocytopenia, which is generally associated with carboplatin use.41 The mechanism for this platelet-protective effect may involve some alteration of megakaryocytopoiesis or thrombocytopoiesis, which could result in increased levels of endogenous thrombopoietin or other cytokines. Ongoing studies are measuring the effect on thrombopoietin. It is also possible that prior exposure to paclitaxel may suppress the inhibition of proplatelet formation, which is associated with carboplatin, when measured in terms of pharmacodynamic effect on platelets.41

To date, the best results with the paclitaxel/carboplatin combination have come from the Fox Chase Cancer Center,26 where a 62% response rate and 54% 1-year survival were noted with paclitaxel (escalating doses, intrapatient, between 135 and 215 mg/m2 with subsequent courses of chemotherapy) and carboplatin (dosed to an area under the plasma concentration-vs-time curve [AUC] of 7.5). Today, the recommended doses for this combination are: paclitaxel 200 mg/m2 to 225 mg/m2 by 3-h or 1-h infusion or 175 mg/m2 by 24-h infusion with carboplatin targeted to an AUC of 6 or 7.

The first large randomized study comparing paclitaxel/carboplatin with standard cisplatin/etoposide therapy in patients with advanced or metastatic NSCLC (Fig 2 ) has been completed, accruing 369 patients in 15 months. The median survival time of the combined group was 8.25 months, and the 1-year survival rate was 35%.42 The number of events required to perform a survival analysis, by study arm, has not been attained, and the results are eagerly awaited. In addition, the paclitaxel/carboplatin combination has become the most widely used regimen for patients with NSCLC in the United States based on the spectrum of activity, the ease of administration, and the wide acceptance by both patients and their treating physicians. This regimen is being investigated further in ongoing randomized cooperative group studies. The controversies regarding the best schedule (24-h vs 3-h vs 1-h) and the optimum dose of paclitaxel in the combination may never be resolved, but further refinement of this regimen by the addition of cytoprotective agents, such as amifostine, to abrogate neuropathy and myelosuppression or growth factors, such as thrombopoetin or megakaryocyte growth and development factor, may prove valuable.



View larger version (20K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Randomized trial of cisplatin/etoposide vs paclitaxel/carboplatin therapy for advanced and metastatic NSCLC: study design.

 

   Docetaxel in NSCLC
TOP
 Abstract
 Introduction
 Paclitaxel in NSCLC
 Docetaxel in NSCLC
References
 
Docetaxel has demonstrated single-agent activity in both chemotherapy-naive patients with advanced NSCLC (Table 7) 43 44 45 46 47 48 49 and in patients whose disease has progressed after or while receiving cisplatin-based regimens (Table 8 ).50 51 52 Myelosuppression is the predominant toxicity observed with docetaxel in all of these studies. Other unique toxicities include nail changes, hypersensitivity reactions, and occasionally symptomatic peripheral edema or effusions.


View this table:
[in this window]
[in a new window]

  		Table 7. Phase II Studies of Docetaxel in Previously Untreated Patients With Advanced NSCLC*

 

View this table:
[in this window]
[in a new window]

  		Table 8. Docetaxel in Previously Treated Patients With Recurrent NSCLC*

 
Docetaxel/Cisplatin Combination in NSCLC
Docetaxel was combined with cisplatin in a multicenter study to evaluate its efficacy against NSCLC. The recommended dose of 75 mg/m2 docetaxel in combination with 75 mg/m2 cisplatin with cycles repeated every 3 weeks53 54 was administered to 47 chemotherapy-naive patients with advanced and metastatic NSCLC.55 The main toxicities observed with this regimen were febrile neutropenia (8.5%), pulmonary toxicity (4.3%), neuromotor effects (2.1%), and asthenia (12.8%). Symptomatic fluid retention occurred in only one patient. Other adverse effects, including nausea, vomiting, diarrhea, and stomatitis, were rare. The observed response rate in this study was 21.3% (95% confidence interval, 10.7 to 35.7%) including one complete response and nine partial responses. The median survival of all patients entered is 10 + months. Based on this activity, the docetaxel/cisplatin combination is being evaluated in an ongoing randomized ECOG study (Fig 2) involving patients with stages IIIB and IV NSCLC.

The combination of docetaxel and cisplatin for NSCLC has been evaluated in three other trials.54 56 57 Zalcberg and colleagues54 used the same dosing schema as in our study (Table 9 ).55 LeChevalier and colleagues56 used a modified regimen of the same combination with a higher cisplatin dose (100 mg/m2) and administered it on a 3-week schedule for the first three cycles, then on a 6-week schedule (Table 10 ). The highest response rate of 48% was noted by Androulakis et al57 (Table 9) ; however, the dose intensity of docetaxel was higher, and all patients received filgrastim support in this study. Thus, the combination of docetaxel and cisplatin appears to be active,55 and confirmation of its activity in the randomized setting is awaited.


View this table:
[in this window]
[in a new window]

  		Table 9. Docetaxel and Cisplatin Combination in NSCLC: Results of Phase II Studies

 

View this table:
[in this window]
[in a new window]

  		Table 10. Docetaxel and Cisplatin Combination in NSCLC: Results of Phase II Studies

 
Docetaxel/Carboplatin Combination in NSCLC
Carboplatin, developed as the less toxic analog of cisplatin, has marginal but consistent activity in patients with NSCLC.58 59 60 61 In a large randomized ECOG study58 comparing three cisplatin-based combination chemotherapy regimens to single-agent carboplatin and iproplatin, the best survival rate was observed on the carboplatin arm. Thus, carboplatin was considered to be suitable for combination with docetaxel.

Phase I Study of Docetaxel and Carboplatin in Advanced Solid Tumors:
A phase I study61 of patients with refractory advanced solid tumors was designed to identify the maximum tolerated dose and toxicity level of docetaxel (with and without filgrastim support) plus carboplatin in combination (Table 11 ). The docetaxel dose was escalated from 65 mg/m2 (cohort 1) to 80 mg/m2 (cohort 2), 90 mg/m2 (cohort 3), and 100 mg/m2 (cohort 4), with each dose followed by carboplatin administration (Table 12 ). The carboplatin dose was targeted to an AUC of 6 using the Calvert formula59 (dose [in milligrams] = target AUC [glomerular filtration rate + 25]). The measured 24-h urinary creatinine clearance was substituted for the glomerular filtration rate. Cycles were repeated every 3 weeks.


View this table:
[in this window]
[in a new window]

  		Table 11. Multicenter Phase II Study of Docetaxel and Carboplatin for Stage IIIB and IV NSCLC: Treatment Regimen

 

View this table:
[in this window]
[in a new window]

  		Table 12. Dose-Escalation Schema for the Phase I Study of Docetaxel/Carboplatin

 
The dose-limiting toxicity on this docetaxel/carboplatin regimen was febrile neutropenia, reached in cohort 3 (docetaxel dose 90 mg/m2); thus, filgrastim was added in cohort 4 (Table 12) . The maximum tolerated doses of docetaxel, with and without filgrastim support, in this combination were 100 mg/m2 and 90 mg/m2, respectively. Other grade 3 toxicities in this study were rare, but included hypotension, GI bleeding, low back pain, nausea, and fatigue. Carboplatin had no effect on docetaxel pharmacokinetics in this study. The authors identified a recommended docetaxel dose of 90 mg/m2 with filgrastim support and 80 mg/m2 without filgrastim support for further evaluation in combination with carboplatin (AUC, 6).

Phase II Trial of Docetaxel and Carboplatin in NSCLC:
Preliminary results from a phase II multicenter study of docetaxel and carboplatin in the treatment of advanced and metastatic NSCLC were presented at the 1997 meeting of the International Association for the Study of Lung Cancer.62 There were 33 patients enrolled and 26 patients evaluable for response in this study; 1 complete response and 14 partial responses were observed in this population, for an overall response rate of 58%. The main toxicities included severe myalgia (15%), asthenia (12%), arthralgia (6%), and febrile neutropenia (12%). The incidence of grade 3/4 neutropenia was 67%, leading the investigators to reduce the dose of carboplatin for the next group of patients to an AUC of 5. Nonetheless, the regimen of docetaxel/carboplatin was considered active against metastatic NSCLC.

Future Directions
The search for new agents and treatment approaches remains an important goal of research in NSCLC. The development of three-drug combination regimens, for example, currently is underway. Newer agents found to be active in NSCLC, such as gemcitabine, vinorelbine, or irinotecan, are being combined with the paclitaxel/carboplatin or the docetaxel/carboplatin combinations. Paclitaxel or docetaxel has been combined with these agents to form nonplatinum doublets, and their activity is being evaluated as well. For the first time, a nonplatinum doublet, paclitaxel/gemcitabine, has been incorporated into the investigational arm of a proposed European Organization for Research and Treatment of Cancer study (Fig 3 ). A large randomized study comparing the docetaxel/carboplatin doublet to the docetaxel/cisplatin and vinorelbine/cisplatin doublets has been initiated. These ongoing studies will provide further insight into the activity and toxicity of combination chemotherapy for NSCLC. With the encouraging results obtained in advanced and metastatic NSCLC, the paclitaxel- and docetaxel-based regimens and combinations are being investigated in earlier stages of the disease, and the results appear to be promising.



View larger version (30K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3. European Organization for Research and Treatment of Cancer randomized study in patients with advanced NSCLC: study design.

 
The taxanes, with their wide spectrum of activity and unique mechanism of action, have sparked a great deal of interest about their use in the management of NSCLC. Ongoing and future investigations will aim to optimize and refine the paclitaxel and docetaxel combinations.


   Footnotes
 
Abbreviations: AUC = area under the plasma concentration-vs-time curve; ECOG = Eastern Cooperative Oncology Group; NSCLC = non-small cell lung cancer


   References
TOP
 Abstract
 Introduction
 Paclitaxel in NSCLC
 Docetaxel in NSCLC
 References
 

  1. Rowinsky, EK, Donehower, RC (1995) Paclitaxel (Taxol). N Engl J Med 332,1004-1014[Free Full Text]
  2. Horwitz, SB (1992) Mechanism of action of Taxol. Trends Pharmacol Sci 13,134-136[CrossRef][Medline]
  3. Chang, AY, Kim, K, Glick, J, et al (1993) Phase II study of Taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results. J Natl Cancer Inst 85,388-394[Abstract/Free Full Text]
  4. Murphy, WK, Fossella, FV, Winn, RJ, et al (1993) Phase II study of Taxol in patients with untreated advanced non-small-cell lung cancer. J Natl Cancer Inst 85,384-388[Abstract/Free Full Text]
  5. Gatzemeier, U, Heckmayer, M, Neuhauss, R, et al (1995) Chemotherapy of advanced inoperable non–small cell lung cancer with paclitaxel: a phase II trial. Semin Oncol 22(suppl),24-28
  6. Millward, MJ, Bishop, JF, Friedlander, M, et al (1996) Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer. J Clin Oncol 14,142-148[Abstract]
  7. Rowinsky, EK, Eisenhauer, EA, Chaudhry, V, et al (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 20(suppl),1-15[ISI][Medline]
  8. Eisenhauer, EA, ten Bokkel Huinink, WW, Swenerton, KD, et al (1994) European–Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol 12,2654-2666[Abstract/Free Full Text]
  9. Hainsworth, JD, Thompson, DS, Greco, FA (1995) Paclitaxel by 1-hour infusion: an active drug in metastatic non-small-cell lung cancer. J Clin Oncol 13,1609-1614[Abstract/Free Full Text]
  10. Akerley, W, Choy, H, Safran, H, et al (1997) Weekly paclitaxel: marked activity, diminished toxicity and platelet stimulating effect [abstract]. Lung Cancer 18(suppl),19
  11. Klastersky, J, Sculier, JP (1995) Cisplatin plus Taxol in non-small cell lung cancer: a dose finding trial [abstract]. Proc Am Assoc Cancer Res Annu Meet 36,A1423
  12. Pirker, R, Krajnik, G, Zochbauer, S, et al (1995) Paclitaxel/cisplatin in advanced non-small cell lung cancer (NSCLC). Ann Oncol 6,833-835[Abstract/Free Full Text]
  13. Belli, L, LeChevalier, T, Gottfried, M, et al (1995) Phase I-II trial of paclitaxel (Taxol) and cisplatin in previously untreated advanced non–small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,350
  14. Rowinsky, EK, Citardi, MJ, Noe, DA, et al (1993) Sequence-dependent cytotoxic effects due to combinations of cisplatin and the antimicrotubule agents Taxol and vincristine. J Cancer Res Clin Oncol 119,727-733[CrossRef][ISI][Medline]
  15. Rowinsky, EK, Gilbert, MR, McGuire, WP, et al (1991) Sequences of Taxol and cisplatin: a phase I and pharmacologic study. J Clin Oncol 9,1692-1703[Abstract]
  16. Bonomi, PD, Kim, K, Chang, A, et al (1996) Phase III trial comparing etoposide (E) cisplatin versus Taxol (T) with cisplatin G-CSF (G) versus cisplatin in advanced non–small cell lung cancer: Eastern Cooperative Oncology Group (ECOG) [abstract]. Proc Am Soc Clin Oncol Annu Meet 15,382
  17. Gelmon, KA, Tolcher, A, O’Reilly, S, et al (1995) Phase I/II trial of biweekly paclitaxel (Taxol) in metastatic breast cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,132
  18. Georgiadis, MS, Brown, JE, Schuler, BS, et al (1995) Phase I study of a four day continuous infusion of paclitaxel followed by cisplatin in patients with advanced lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,353
  19. Bonomi, PD, Finkelstein, DM, Ruckdeschel, JC, et al (1989) Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non–small cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 7,1602-1613[Abstract]
  20. Kramer, BS, Birch, R, Greco, A, et al (1988) Randomized phase II evaluation of iproplatin (CHIP) and carboplatin (CBDCA) in lung cancer. Am J Clin Oncol 11,643-645[ISI][Medline]
  21. Kreisman, H, Ginsberg, S, Propert, KJ, et al (1987) Carboplatin or iproplatin in advanced non–small cell lung cancer: a Cancer and Leukemia Group B study. Cancer Treat Rep 71,1049-1052[ISI][Medline]
  22. Gandara, DR, Wold, H, Perez, EA, et al (1989) Cisplatin dose intensity in non–small cell lung cancer: phase II results of a day 1 and day 8 high-dose regimen. J Natl Cancer Inst 81,790-794[Abstract/Free Full Text]
  23. Wozniak, AJ, Crowley, JJ, Balcerzak, SP, et al (1996) Randomized phase III trial of cisplatin (CDDP) vs. CDDP plus navelbine (NVB) in treatment of advanced non–small cell lung cancer (NSCLC): report of a Southwest Oncology Group study (SWOG-9308) [abstract]. Proc Am Soc Clin Oncol Annu Meet 15,374
  24. Klastersky, J, Sculier, JP, Bureau, G, et al (1989) Cisplatin versus cisplatin plus etoposide in the treatment of advanced non–small cell lung cancer. J Clin Oncol 7,1087-1092[Abstract]
  25. Belani, CP, Aisner, J, Hiponia, D, et al (1996) Paclitaxel and carboplatin in metastatic non–small cell lung cancer: preliminary results of a phase I study. Semin Oncol 23(suppl),19-21
  26. Langer, CJ, Leighton, JC, Comis, RL, et al (1995) Paclitaxel and carboplatin in combination in the treatment of advanced non–small cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol 13,1860-1870[Abstract/Free Full Text]
  27. Johnson, DH, Paul, DM, Hande, KR, et al (1996) Paclitaxel plus carboplatin in advanced non–small cell lung cancer: a phase II trial. J Clin Oncol 14,2054-2060[Abstract/Free Full Text]
  28. Lee, FH, Cabetta, R, Ussekk, BF, et al (1983) New platinum complexes in clinical trials. Cancer Treat Rev 10,43-45
  29. Canetta, R, Franks, C, Smaldone, L, et al (1987) Clinical status of carboplatin. Oncology 1,61-69
  30. Bonomi, PD, Finkelstein, DM, Ruckdeschel, JC, et al (1989) Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group (ECOG). J Clin Oncol 7,1602-1613
  31. Bunn, PA, Jr (1989) Review of therapeutic trials of carboplatin in lung cancer. Semin Oncol 16(suppl),27-33
  32. Natale, RB (1996) Preliminary results of a phase I/II clinical trial of paclitaxel and carboplatin in non–small cell lung cancer. Semin Oncol 23(suppl),2-6[ISI][Medline]
  33. Rowinsky, EK, Flood, WA, Sartorius, SE, et al (1995) Phase I study of paclitaxel as a 3-hour infusion followed by carboplatin in untreated patients with stage IV non–small cell lung cancer. Semin Oncol 22(suppl),48-54[ISI][Medline]
  34. Schutte, W, Bork, I, Sucker, S (1996) Phase II trial of paclitaxel and carboplatin as firstline treatment in advanced non–small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol Annu Meet 15,398
  35. Bunn, PA, Jr, Kelly, K (1995) A phase I study of carboplatin and paclitaxel in non–small cell lung cancer: a University of Colorado Cancer Center study. Semin Oncol 22(suppl),2-6
  36. Giaccone, G, Huizing, M, Postmus, PE, et al (1995) Dose-finding and sequencing study of paclitaxel and carboplatin in non–small cell lung cancer. Semin Oncol 22,78-82
  37. Hainsworth, JD, Thompson, DS, Urba, WJ, et al (1996) One hour paclitaxel plus carboplatin in advanced non–small cell lung cancer (NSCLC): preliminary results of a multi-institutional phase II study [abstract]. Proc Am Soc Clin Oncol Annu Meet 15,379
  38. Langer, C, Kaplan, R, Rosvold, E, et al (1996) Paclitaxel (P) by 1 hour (hr) infusion combined with carboplatin (C) in advanced non–small cell lung carcinoma [abstract]. Proc Am Soc Clin Oncol Annu Meet 15,396
  39. Roa, V, Conner, A, Mitchell, RB (1996) Carboplatin and paclitaxel for chemotherapy-naive patients with advanced non–small cell lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 15,404
  40. Evans, WK, Stewart, DJ, Tomiak, E, et al (1995) Carboplatin (C) and paclitaxel (P) by one hour infusion for advanced non–small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,374
  41. Kearns, CM, Belani, CP, Erkmen, K, et al (1995) Reduced platelet toxicity with combination carboplatin and paclitaxel; pharmacodynamic modulation of carboplatin associated thrombocytopenia [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,170
  42. Belani, CP, Natale, R, Lee, JS, et al (1998) Randomized study of cisplatin/etoposide versus paclitaxel/carboplatin in advanced and metastatic non–small cell lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 17,455a
  43. Cerny, T, Kaplan, S, Pavlidis, N, et al (1994) Docetaxel (Taxotere) is active in non–small cell lung cancer: a phase II trial of the EORTC early clinical trials group (ECTG). Br J Cancer 70,384-387[ISI][Medline]
  44. Francis, PA, Rigas, JR, Kris, MG, et al (1994) Phase II trial of docetaxel in patients with stage III and IV non–small cell lung cancer. J Clin Oncol 12,1232-1237[Abstract/Free Full Text]
  45. Burris, HA, Eckardt, J, Fields, S, et al (1993) Phase II trials of taxotere in patients with non–small cell lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 12,335
  46. Fossella, FV, Lee, JS, Murphy, WK, et al (1994) Phase II study of docetaxel for recurrent or metastatic non–small cell lung cancer. J Clin Oncol 12,1238-1244[Abstract/Free Full Text]
  47. Watanabe, K, Yokoyama, A, Furuse, K, et al (1994) Phase II trial of docetaxel in previously untreated non–small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol Annu Meet 13,331
  48. Miller, VA, Rigas, JR, Francis, PA, et al (1995) Phase II trial of a 75 mg/m2 dose of docetaxel with prednisone premedication for patients with advanced non–small lung cancer. Cancer 75,968-972[CrossRef][ISI][Medline]
  49. Lira-Puerto, V, Zepeda, G, Mohar, A, et al (1995) Phase-II trial of Taxotere (docetaxel) in advanced non–small cell lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,382
  50. Burris, H, Eckardt, J, Fields, S, et al (1993) Phase II trials of Taxotere in patients with non–small cell lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 12,338
  51. Fossella, FV, Lee, JS, Shin, DM, et al (1995) Phase II study of docetaxel (Taxotere) for advanced or metastatic platinum-refractory non–small cell lung cancer. J Clin Oncol 13,645-651[Abstract/Free Full Text]
  52. Gandara, DR, Vokes, E, Green, M, et al (1996) Docetaxel (Taxotere) in platinum-treated non–small cell lung cancer (NSCLC): confirmation of prolonged survival in a multicenter trial [abstract]. Proc Am Soc Clin Oncol Annu Meet 16,508
  53. Pronk, LC, Schellens, JH, Planting, AS, et al (1997) Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. J Clin Oncol 15,1071-1091[Abstract/Free Full Text]
  54. Zalcberg, JR, Bishop, JF, Millward, MJ, et al (1995) Interim results of a phase II trial of docetaxel in combination with cisplatin in patients with metastatic or locally advanced non–small cell lung cancer (NSCLC) [abstract]. Eur J Cancer 31A(suppl),S226
  55. Belani, CP, Bonomi, P, Dobbs, T, et al (1997) Multicenter phase II trial of docetaxel and cisplatin combination in patients with non–small cell lung cancer [abstract]. Proc Am Soc Clin Oncol Annu Meet 16,221a
  56. LeChevalier, T, Belli, L, Monnier, A, et al (1995) Phase II study of docetaxel (Taxotere) and cisplatin in advanced non–small cell lung cancer (NSCLC): an interim analysis [abstract]. Proc Am Soc Clin Oncol Annu Meet 14,350
  57. Androulakis, N, Dimopoulos, AM, Kourousis, C, et al (1997) First-line treatment of advanced non–small cell lung cancer (NSCLC) with docetaxel and cisplatin: a multicenter phase II study [abstract]. Proc Am Soc Clin Oncol Annu Meet 16,461a
  58. Bonomi, PD, Finkelstein, DM, Ruckdeschel, JC, et al (1989) Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non–small cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 7,1602-1613
  59. Calvert, AH, Harland, SJ, Newell, DR, et al (1982) Early clinical studies with cis-diammine-1, 1 cyclobutane-decarboxylate platinum II. Cancer Chemother Pharmacol 9,140-147[CrossRef][ISI][Medline]
  60. Curt, GA, Grygeil, JJ, Corden, BJ, et al (1983) A phase I and pharmacokinetic study of diammine-cyclobutane-decarboxylate-platinum (NSC 241240). Cancer Res 43,4470-4473[Abstract/Free Full Text]
  61. Belani, CP, Hadeed, V, Ramanathan, R, et al (1997) Docetaxel and carboplatin: a phase I and pharmacokinetic trial for advanced non-hematologic malignancies [abstract]. Proc Am Soc Clin Oncol Annu Meet 16,220a
  62. Belani, CP, Einzig, A, Bonomi, P, et al (1997) Multi-institutional phase II trial of docetaxel and carboplatin combination in patients with stage IIIB and IV non–small cell lung cancer (NSCLC) [abstract]. Lung Cancer 18,16



This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
N. V. Koshkina, J. C. Waldrep, L. E. Roberts, E. Golunski, S. Melton, and V. Knight
Paclitaxel Liposome Aerosol Treatment Induces Inhibition of Pulmonary Metastases in Murine Renal Carcinoma Model
Clin. Cancer Res., October 1, 2001; 7(10): 3258 - 3262.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Belani, C. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Belani, C. P.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS