0
Clinical Investigations: Miscellaneous |

Neoadjuvant Etoposide, Ifosfamide, and Cisplatin Followed by Concomitant Thoracic Radiotherapy and Continuous Cisplatin Infusion in Stage IIIb Non-small Cell Lung Cancer*

Jean-Louis Pujol, MD; Thierry Lafontaine, MD; Xavier Quantin, MD; Monique Reme-Saumon, MD; Didier Cupissol, MD, PhD; Farid Khial, PhD; François-Bernard Michel, MD
Author and Funding Information

*From the Department of Respiratory Diseases (Drs. Pujol, Lafontaine, Quantin, Khial, and Michel), Hôpital Arnaud de Villeneuve, and the Cancer Institute (Drs. Lafontaine, Reme-Saumon, and Cupissol), Centre Val d’Aurelle, Montpellier, France.



Chest. 1999;115(1):144-150. doi:10.1378/chest.115.1.144
Text Size: A A A
Published online

Objective: To determine the applicability and safety of an ifosfamide, cisplatin, and etoposide (VIP) regimen as a neoadjuvant chemotherapy to a concomitant thoracic radiotherapy and cisplatin continuous infusion in locally advanced non-small cell lung cancer (NSCLC).

Patients and methods: Forty-four patients (stage IIIb in 43 and stage IIIa in 1) entered a study of VIP, followed by concomitant thoracic radiotherapy and cisplatin continuous infusion. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection), and etoposide 100 mg/m2 given on days 1 to 4 of a 21-day cycle with hematopoietic support using recombinant human methionyl granulocyte colony stimulating factor. Patients who achieved a response or a stabilization were planned to receive a split-course normofractionated thoracic radiotherapy (first course: 30 Gy/10; 4-week rest period; second course: 25 Gy/10). A continuous cisplatin infusion of 6 mg/m2 daily was administered using an autonomous chemotherapy delivery device. Total plasma platinum titration was performed daily during the two courses in five of the patients. Analyses were done on an intent-to-treat basis.

Results: Thirty-nine of the 44 patients received the three-cycle chemotherapy program. Received dose intensity was 82%. Thirty-eight patients received the radiotherapy and, among them, 35 received the complete concomitant continuous cisplatin infusion. Objective (complete) response rates were 48% (7%) at the end of chemotherapy and increased up to 61% (16%) by the end of radiotherapy. At the end of the first radiotherapy cycle, the mean total plasma platinum concentration was twice as high as that of the residual postinduction chemotherapy concentration. During induction chemotherapy, myelosuppression was the limiting toxicity requiring hospital readmission in 23 patients. During radiotherapy, the main toxicity was acute esophagitis. A relatively high rate of pulmonary fibrosis was observed using the subjective objective management analytic—late effects of normal tissue score without life-threatening pulmonary function impairment. None of the patients died from toxic reactions. Probability of survival at 1, 2, and 3 years was 49%, 19%, and 5%, respectively. Primary cause of failure was a local relapse in 63% of the patients, brain metastases in 24%, and hematogeneous metastases to other sites in 13%.

Conclusion: Neoadjuvant VIP followed by concomitant radiotherapy-chemotherapy is feasible, but the split-course radiotherapy did not prevent a high rate of local recurrences. The high rate of toxic reactions requiring hospital readmission limits further development of such an aggressive regimen in NSCLC.

Abbreviations: CAP = cisplatin, doxorubicin (Adriamycin), cyclophosphamide; CI = confidence interval; MVP = mitomycin C, vinblastine or vindesine, cisplatin; NSCLC = non-small cell lung cancer; r-metHuG-CSF = recombinant human methionyl granulocyte colony stimulating factor; SOMA-LENT = subjective objective management analytic—late effects of normal tissues; VIP = cisplatin, etoposide, ifosfamide combination; WHO = World Health Organization

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
Methemoglobinemia After Infusion of Ifosfamide Chemotherapy*: First Report of a Potentially Serious Adverse Reaction Related to Ifosfamide
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543