Combination Chemotherapy and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

Condition(s) targeted: Drug Toxicity; Lung Cancer; Radiation Toxicity

Intervention: amifostine trihydrate (Drug); cisplatin (Drug); etoposide (Drug); filgrastim (Drug); paclitaxel (Drug); topotecan hydrochloride (Drug); biological therapy (Procedure); chemoprotection (Procedure); chemotherapy (Procedure); colony-stimulating factor therapy (Procedure); cytokine therapy (Procedure); radiation therapy (Procedure); radioprotection (Procedure); supportive care/therapy (Procedure)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: North Central Cancer Treatment Group

Official(s) and/or principal investigator(s):
Scott Okuno, MD, Study Chair, Affiliation: Mayo Clinic

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy before, during, and after radiation therapy in treating patients who have limited-stage small cell lung cancer.

Official title: Phase I-II Study of Topotecan and Paclitaxel Followed by High-Dose Thoracic Radiation Therapy With Concomitant Cisplatin/Etoposide and Amifostine in Limited-Stage Small Cell Lung Cancer

Study design: Interventional, Treatment

Primary outcome: Survival at 2 years

Secondary outcome:

Local progression-free survival at 2 years

Tolerabiltiy and toxicity

Overall survival

Time to progression

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of thoracic radiotherapy administered with cisplatin, etoposide, and amifostine preceded and followed by topotecan and paclitaxel in patients with limited stage small cell lung cancer (phase I closed to accrual as of 5/27/2004).

* Determine the two-year survival of this patient population treated with this regimen.

* Determine the two-year, progression-free local control rate in this patient population treated with this regimen.

* Assess the tolerability of this treatment regimen in these patients.

* Determine the antitumor activity of this regimen in these patients.

* Determine the overall survival and overall time to progression in this patient population treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of thoracic radiotherapy (TRT).

Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 5. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 24 hours after the last dose of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 2 courses.

After 2 courses of topotecan and paclitaxel, patients undergo TRT twice daily for 5 consecutive days for 5 weeks. During TRT, patients receive cisplatin IV, oral etoposide, and amifostine SC daily prior to TRT.

At 4 weeks after completion of TRT, patients receive 2 additional courses of topotecan, paclitaxel, and G-CSF every 3 weeks followed by prophylactic cranial irradiation.

Cohorts of 3-6 patients receive escalating doses of TRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity (phase I closed to accrual as of 5/27/2004).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 3-73 patients will be accrued for this study (phase I closed to accrual as of 5/27/2004).

Minimum age: 18 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed small cell lung cancer

* Limited disease confined to one hemithorax, the ipsilateral supraclavicular fossa, and encompassable within tolerable thoracic radiotherapy field

- Minimal pleural effusions (i. e., blunting of the costophrenic angle on chest x-ray or a small effusion on CT scan) allowed

* Measurable disease

- At least one lesion accurately measured in at least 1 dimension with longest diameter at least 20 mm

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm^3

* Platelet count at least 100,000/mm^3

Hepatic:

* Bilirubin no greater than 1. 5 times upper limit of normal (ULN)

* AST no greater than 3 times ULN

Renal:

* Creatinine no greater than 1. 5 times ULN

Cardiovascular:

* No New York Heart Association class III or IV heart disease

Pulmonary:

* FEV_1 at least 40% of predicted AND at least 1 liter

Other:

* No uncontrolled infection

* No other severe underlying diseases

* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas (carcinoma in situ)

* No grade 2 or greater peripheral neuropathy

* Not pregnant or nursing

* Negative pregnancy test

* Fertile patients must use effective contraception

* No hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any excipients of G-CSF

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* No prior hemithorax radiotherapy

Surgery

* Not specified

Other

* No prior therapy for small cell lung cancer

CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale, Arizona 85259, United States

Mayo Clinic - Jacksonville, Jacksonville, Florida 32224-9980, United States

BroMenn Regional Medical Center, Normal, Illinois 61761, United States

Cancer Treatment Center at Pekin Hospital, Pekin, Illinois 61554, United States

Carle Cancer Center at Carle Foundation Hospital, Urbana, Illinois 61801, United States

CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States

CCOP - Illinois Oncology Research Association, Peoria, Illinois 61615, United States

Community Cancer Center, Normal, Illinois 61761, United States

Community Hospital of Ottawa, Ottawa, Illinois 61350, United States

Eureka Community Hospital, Eureka, Illinois 61530, United States

Galesburg Clinic, Galesburg, Illinois 61401, United States

Galesburg Cottage Hospital, Galesburg, Illinois 61401, United States

Graham Hospital, Canton, Illinois 61520, United States

Hopedale Medical Complex, Hopedale, Illinois 61747, United States

Illinois Valley Community Hospital, Peru, Illinois 61354, United States

InterCommunity Cancer Center of Western Illinois, Galesburg, Illinois 61401, United States

Joliet Oncology Hematology Associates, Limited - West, Joliet, Illinois 60435, United States

Kewanee Hospital, Kewanee, Illinois 61443, United States

Mason District Hospital, Havana, Illinois 62644, United States

McDonough District Hospital, Macomb, Illinois 61455, United States

Memorial Hospital, Carthage, Illinois 62321, United States

Methodist Medical Center of Illinois, Peoria, Illinois 61603, United States

Oncology Hematology Associates of Central Illinois - Ottawa, Ottawa, Illinois 61350, United States

Oncology/Hematology Associates of Central Illinois, P.C., Peoria, Illinois 61615, United States

OSF St. Francis Medical Center, Peoria, Illinois 61637, United States

Perry Memorial Hospital, Princeton, Illinois 61356, United States

Proctor Hospital, Peoria, Illinois 61614, United States

Rush-Copley Cancer Care Center, Aurora, Illinois 60507, United States

St. Joseph Medical Center, Bloomington, Illinois 61701, United States

St. Margaret's Hospital, Spring Valley, Illinois 61362, United States

Valley Cancer Center, Spring Valley, Illinois 61362, United States

Saint Anthony Memorial Health Centers, Michigan City, Indiana 46360, United States

Cedar Rapids Oncology Associates, Cedar Rapids, Iowa 52403, United States

McFarland Clinic, P.C., Ames, Iowa 50010, United States

Mercy Cancer Center at Mercy Medical Center - North Iowa, Mason City, Iowa 50401, United States

Mercy Cancer Center at Mercy Medical Center, Cedar Rapids, Iowa 52403, United States

Mercy Medical Center - Sioux City, Sioux City, Iowa 51104, United States

Siouxland Hematology-Oncology Associates, Sioux City, Iowa 51101, United States

Siouxland Regional Cancer Center, Sioux City, Iowa 51101-1733, United States

St. Luke's Hospital, Cedar Rapids, Iowa 52402, United States

St. Luke's Regional Medical Center, Sioux City, Iowa 51104, United States

Associates in Womens Health, Wichita, Kansas 67203, United States

Cancer Center of Kansas - Chanute, Chanute, Kansas 66720, United States

Cancer Center of Kansas - Dodge City, Dodge City, Kansas 67801, United States

Cancer Center of Kansas - Kingman, Kingman, Kansas 67068, United States

Cancer Center of Kansas - Newton, Newton, Kansas 67114, United States

Cancer Center of Kansas - Salina, Salina, Kansas 67042, United States

Cancer Center of Kansas - Wellington, Wellington, Kansas 67152, United States

Cancer Center of Kansas - Winfield, Winfield, Kansas 67156, United States

Cancer Center of Kansas, P.A. - Wichita, Wichita, Kansas 67214, United States

Cancer Center of Kansas, P.A. - El Dorado, El Dorado, Kansas 67042, United States

Cancer Center of Kansas, P.A. - Parsons, Parsons, Kansas 67357, United States

Cancer Center of Kansas, P.A., Wichita, Kansas 67208, United States

CCOP - Wichita, Wichita, Kansas 67214, United States

Pratt Cancer Center of Kansas, Pratt, Kansas 67124, United States

Southwest Medical Center, Liberal, Kansas 67901, United States

Via Christi Cancer Center at Via Christi Regional Medical Center, Wichita, Kansas 67214, United States

Wesley Medical Center, Wichita, Kansas 67214, United States

CCOP - Michigan Cancer Research Consortium, Ann Arbor, Michigan 48100, United States

Genesys Hurley Cancer Institute, Flint, Michigan 48532, United States

Hurley Medical Center, Flint, Michigan 48502, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center, Dearborn, Michigan 48123, United States

Seton Cancer Institute - Saginaw, Saginaw, Michigan 48601, United States

St. John Macomb Hospital, Warren, Michigan 48903, United States

St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital, Ann Arbor, Michigan 48106-0995, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

MeritCare Clinic - Bemidji, Bemidji, Minnesota 56601, United States

Bryan LGH Medical Center West, Lincoln, Nebraska 68502, United States

Cancer Resource Center - Lincoln, Lincoln, Nebraska 68510, United States

St. Elizabeth Regional Medical Center, Lincoln, Nebraska 68510, United States

Altru Cancer Center at Altru Hospital, Grand Forks, North Dakota 58201, United States

Bismarck Cancer Center, Bismarck, North Dakota 58501, United States

Cancer Care Center at Medcenter One Hospital, Bismarck, North Dakota 58501, United States

CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States

MeritCare Medical Group, Fargo, North Dakota 58122, United States

Mid Dakota Clinic, P.C., Bismarck, North Dakota 58501, United States

St. Alexius Medical Center, Bismarck, North Dakota 58501, United States

Geisinger Medical Center, Danville, Pennsylvania 17822-2001, United States

Geisinger Medical Group, State College, Pennsylvania 16801, United States

Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania 18711, United States

Avera McKennan Hospital and University Health Center, Sioux Falls, South Dakota 57105, United States

Medical X-Ray Center, Sioux Falls, South Dakota 57105, United States

Sioux Valley Hospital and University of South Dakota Medical Center, Sioux Falls, South Dakota 57104, United States

Franciscan Skemp Healthcare, La Crosse, Wisconsin 54601, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Related publications:

Garces YI, Okuno SH, Schild SE, Mandrekar SJ, Bot BM, Martens JM, Wender DB, Soori GS, Moore DF Jr, Kozelsky TF, Jett JR. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):995-1001.

Starting date: February 2001
Last updated: March 13, 2007