Bladder Cancer
Conditions
Keywords
stage II bladder cancer, stage III bladder cancer, transitional cell carcinoma of the bladder
Brief summary
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation therapy regimens to see how they work in treating patients with stage II or stage III bladder cancer that was removed by surgery.
Detailed description
OBJECTIVES: Primary * To estimate the rate of distant metastasis at 3 years in patients who have undergone transurethral resection of the bladder tumor for stage II or III muscle-invasive bladder cancer treated with chemoradiotherapy comprising fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and radiotherapy followed by selective bladder preservation and adjuvant chemotherapy comprising gemcitabine hydrochloride and cisplatin. Secondary * To estimate the treatment completion rate in these patients. * To estimate acute and late grade toxicities (≥ grade 3 genitourinary, gastrointestinal, and hematologic toxicities) of these regimens in these patients. * To estimate the efficacy of these regimens, in terms of achieving complete response of the primary tumor, in these patients. * To estimate the efficacy of these regimens, in terms of preserving the native, tumor-free bladder 5 years after completion of therapy, in these patients. * To estimate the value of tumor histopathologic, molecular genetic, DNA content, metabolomic, and proteomic parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival. * To analyze for American Urological Association (AUA) Symptom scores at baseline and at 3 years from patients on both arms. * To find potentially predictive biomarkers for cystectomy-free survival. * To find potentially predictive biomarkers for acute and late toxicities. OUTLINE: This is a multicenter study. Patients are stratified according to tumor stage (T2 vs T3-4a). Patients are randomized to 1 of 2 treatment arms.
Interventions
15 mg/m\^2 administered as a 60-minute infusion on days 1,2,3,8,9,10,15,16,17.
DRUGinduction 5-fluorouracil
400mg/m\^2 administered as a 24-hour infusion on days 1,2,3, and 15,16,17.
DRUGinduction gemcitabine
27 mg/m\^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15, 18, 22, 25.
RADIATIONInduction BID radiation therapy
Twice daily (BID) on days 1-5,8-12,15-17. The first daily treatment consists of 1.6 Gy delivered to the pelvis. The second fraction consists of 1.5 Gy to the bladder for the first 5 treatment days. Then, 1.5 Gy is delivered to bladder tumor volume as the second treatment for the remaining 8 treatment days. The bladder tumor volume receives a total of 40.3 Gy.
RADIATIONInduction QD radiation therapy
Once daily (QD) on days (1-5,8-12,15-19,22-26). For the first 10 treatment days, 2 Gy is delivered to the pelvis. Then, 2 Gy is delivered to the bladder for the next 4 treatment days, followed by 2 Gy to the bladder tumor volume for the remaining 6 treatment days. The bladder tumor volume receives a total of 40 Gy.
RADIATIONConsolidation BID radiation therapy
Twice daily (BID) for 8 days on days 1,2,3,4,5,8,9,10 of consolidation. 1.5 Gy per fraction for a total of 24 Gy delivered to the pelvis.
RADIATIONConsolidation QD radiation therapy
Once daily (QD) pelvic radiation therapy for 12 days on days 1-5,8-12,15-16 of consolidation. 2 Gy per fraction for a total of 24 Gy delivered to the pelvis.
DRUGconsolidation gemcitabine
27 mg/m\^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15 of consolidation.
DRUGconsolidation 5-fluorouracil
400 mg/m\^2 administered as a 24-hour infusion on days 1, 2, 3 and 8, 9, 10 of consolidation.
DRUGconsolidation cisplatin
15 mg/m\^2 administered as a sixty-minute infusion on days 1, 2, 8, 9 of consolidation.
PROCEDUREradical cystectomy
Operable patients who have a pT1 or worse tumor response on re-evaluation following initial transurethral resection and induction chemoradiotherapy will have a radical cystectomy 3-8 weeks following the post-induction response evaluation.
PROCEDUREPost-Induction Chemoradiotherapy Endoscopic Response Evaluation
Urine cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination after biopsy.
DRUGadjuvant gemcitabine
1000 mg/m\^2 administered intravenously over 30-60 minutes (preferably 30 minutes) on days 1 and 8 of each 21-day cycle for four cycles.
70 mg/m\^2 administered as a sixty-minute infusion on day 1 of each 21-day cycle for four cycles.
Sponsors
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Pathologically (histologically or cytologically) proven diagnosis of primary carcinoma of the bladder (transitional cell cancer) within 8 weeks of registration. Operable patients whose tumors are primary carcinomas of the bladder and exhibit histologic evidence of muscularis propria invasion and are American Joint Committee on Cancer (AJCC) clinical stages T2-T4a, Nx or N0, M0 (Appendix IV) without hydronephrosis; patients who have involvement of the prostatic urethra with transitional cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible. T2a, T2b, T3a, T3b -substages‖ are not usually able to be determined with clinical (TURBT) staging. 2. If radiologic evaluation of a lymph node is interpreted as positive, this must be evaluated further either by lymphadenectomy or percutaneous needle biopsy. Patients with histologically or cytologically confirmed node metastases will not be eligible. 3. Patients must have an adequately functioning bladder after thorough evaluation by an urologist and have undergone as thorough a transurethral resection of the bladder tumor as is judged safely possible. 4. Patients must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy by the joint agreement of the participating Urologist, Radiation Oncologist, and Medical Oncologist. 5. History and physical examination including weight, performance status, and body surface area within 8 weeks prior to study registration 6. Zubrod Performance Status ≤ 1 7. Age ≥ 18 8. Complete blood count (CBC)/differential obtained no more than 4 weeks prior to registration on study, with adequate bone marrow function defined as follows: * 8.1 White blood cell count (WBC) ≥ 4000/ml * 8.2 Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3; * 8.3 Platelets ≥ 100,000 cells/mm3; * 8.4 Hemoglobin (hgb) ≥ 10.0 mg/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.); 9. Serum creatinine of 1.5 mg% or less; serum bilirubin of 2.0 mg% or less; creatinine clearance of 60 ml/min or greater no more than 4 weeks prior to registration; Note: Calculated creatinine clearance is permissible. If the creatinine clearance is \> 60 ml/min, then a serum creatinine of up to 1.8 mg% is allowable at the discretion of the study chair; 10. Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior to study entry; women of childbearing potential and male participants must practice adequate contraception. 11. Patient must be able to provide study-specific informed consent prior to study entry.
Exclusion criteria
1. Evidence of tumor-related hydronephrosis 2. Evidence of distant metastases or histologically or cytologically proven lymph node metastases 3. Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy 4. A prior or concurrent malignancy of any other site or histology unless the patient has been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix 5. Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease 6. Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside) 7. Severe, active co-morbidity, defined as follows: * 7.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; * 7.2 Transmural myocardial infarction within the last 6 months; * 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; * 7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; * 7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol. * 7.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients. 8. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. 9. Prior allergic reaction to the study drug(s) involved in this protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Without Distant Metastases by Three Years | From randomization to three years | Distant metastasis occurrence is defined as the first appearance of disease (with radiographic evidence) in a non-regional lymph node, solid organ or bone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events | From start of treatment to 180 days after the end of treatment. Treatment could last up to 40 weeks depending on arm, tumor response, and allowed time ranges. | Highest grade adverse event (AE) per subject was counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. All adverse events are counted, regardless of reported relationship to protocol treatment. |
| Number of Patients Experiencing Complete Response of the Primary Tumor After Induction Therapy | 3-4 weeks following induction therapy (approximately maximum 8 weeks from start of treatment depending on treatment arm and allowed time windows) | Patients will be considered as having a clinical complete response when all biopsies are negative at the site(s) of the pretreatment tumor(s). |
| Number of Participants With Progression or Removal of Bladder Five Years After Therapy | From start of treatment to five years after the end of therapy. Treatment could last up to 40 weeks depending on arm, tumor response, and allowed time ranges. | Progression is defined as an increase of 50% or more in the largest diameter of the endoscopically appreciable tumor in the tumor-site biopsy specimen, the development of new bladder tumors, or the development of metastatic disease. |
| Percentage of Patients Who Completed Treatment Per Protocol | After each treatment component (induction, consolidation, adjuvant). Timing varies bases on arm, tumor response at multiple time points, and allowed time ranges. | Treatment administration data was centrally reviewed to determine if patients completed each treatment component per protocol. |
| Determining Potentially Predictive Biomarkers for Acute and Late Toxicities | The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this out | — |
| Determining Potentially Predictive Biomarkers for Cystectomy-free Survival | The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this out | — |
| Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Baseline and 3 years | The AUASI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as 3-year score - baseline score such that a negative change indicates improvement. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5-FU and Cisplatin + BID Irradiation Within 8 weeks following pre-study transurethral resection (TUR) patients receive 2.5 weeks of induction chemoradiotherapy (induction 5-fluorouracil, induction cisplatin, induction BID radiation therapy). Consolidation chemoradiotherapy begins 7-14 days following post-induction chemoradiotherapy endoscopic response evaluation. Patients achieving a complete response receive 1.5 weeks of consolidation chemoradiotherapy (consolidation 5-fluorouracil, consolidation cisplatin, consolidation BID radiation therapy). Patients without a complete response undergo radical cystectomy. Outpatient adjuvant chemotherapy (adjuvant gemcitabine, adjuvant cisplatin) begins 4-5 weeks following the post-consolidation endoscopic evaluation or 8-12 weeks following radical cystectomy, and continues for 12 weeks. | 33 |
| Gemcitabine + QD Irradiation Within 8 weeks following pre-study transurethral resection (TUR) patients receive 2.5 weeks of induction chemoradiotherapy (induction gemcitabine and induction QD radiation therapy). Consolidation chemoradiotherapy begins 7-14 days following post-induction chemoradiotherapy endoscopic response evaluation. Patients achieving a complete response receive 1.5 weeks of consolidation chemoradiotherapy (consolidation gemcitabine and consolidation QD radiation therapy). Patients without a complete response undergo radical cystectomy. Outpatient adjuvant chemotherapy (adjuvant gemcitabine and adjuvant cisplatin) begins 4-5 weeks following the post-consolidation endoscopic evaluation or 8-12 weeks following radical cystectomy, and continues for 12 weeks. | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive any protocol treatment | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | 5-FU and Cisplatin + BID Irradiation | Gemcitabine + QD Irradiation | Total |
|---|---|---|---|
| Age, Customized <= 49 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Customized 50-59 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Customized 60-69 years | 13 Participants | 20 Participants | 33 Participants |
| Age, Customized >= 70 years | 13 Participants | 9 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 33 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 29 Participants | 59 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 50 Participants |
| T Stage cT2 | 32 Participants | 32 Participants | 64 Participants |
| T Stage cT3-T4a | 1 Participants | 1 Participants | 2 Participants |
| Zubrod Performance Status 0 | 29 Participants | 32 Participants | 61 Participants |
| Zubrod Performance Status 1 | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 33 | 11 / 33 |
| other Total, other adverse events | 33 / 33 | 33 / 33 |
| serious Total, serious adverse events | 11 / 33 | 8 / 33 |
Outcome results
Primary
Percentage of Patients Without Distant Metastases by Three Years
Distant metastasis occurrence is defined as the first appearance of disease (with radiographic evidence) in a non-regional lymph node, solid organ or bone.
Time frame: From randomization to three years
Population: Eligible patients with 3-year data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5-FU and Cisplatin + BID Irradiation | Percentage of Patients Without Distant Metastases by Three Years | 77.8 percentage of participants |
| Gemcitabine + QD Irradiation | Percentage of Patients Without Distant Metastases by Three Years | 84.0 percentage of participants |
Comparison: The confidence interval of the rate was calculated by Clopper-Pearson's exact binomial confidence intervals methods with one-sided type I error of 0.1. The study required 32 analyzable patients in each arm, which would warrant a 10% chance of observing a percentage of patients without distant metastasis by 3 years of less than 75% if the true rate was 86%. With the actual number of evaluable patients, the study instead warrants a 13-14% chance.
Secondary
Change in American Urological Association Symptom Index (AUASI) Score at 3 Years
The AUASI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as 3-year score - baseline score such that a negative change indicates improvement.
Time frame: Baseline and 3 years
Population: Eligible patients with baseline and 3-year scores
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Sensation of Not Emptying Bladder | -0.50 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Weak Urinary Stream | -0.50 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Stopped and Started When Urinating | -1.00 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Push or Strain to Begin Urination | -0.50 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Urinate Again < 2 Hours After Urinating | -2.50 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | How Often Get Up at Night to Urinate | -3.50 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Difficult to Postpone Urination | -3.00 units on a scale |
| 5-FU and Cisplatin + BID Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | AUA Total Symptom Score | -9.50 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Difficult to Postpone Urination | -0.50 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Sensation of Not Emptying Bladder | 0.0 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Urinate Again < 2 Hours After Urinating | -1.0 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Stopped and Started When Urinating | 0.00 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | AUA Total Symptom Score | -3.50 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Weak Urinary Stream | 0.00 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | Push or Strain to Begin Urination | 0.00 units on a scale |
| Gemcitabine + QD Irradiation | Change in American Urological Association Symptom Index (AUASI) Score at 3 Years | How Often Get Up at Night to Urinate | -1.50 units on a scale |
Secondary
Determining Potentially Predictive Biomarkers for Acute and Late Toxicities
Time frame: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this out
Population: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from our tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.
Secondary
Determining Potentially Predictive Biomarkers for Cystectomy-free Survival
Time frame: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this out
Population: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from our tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.
Secondary
Number of Participants With Progression or Removal of Bladder Five Years After Therapy
Progression is defined as an increase of 50% or more in the largest diameter of the endoscopically appreciable tumor in the tumor-site biopsy specimen, the development of new bladder tumors, or the development of metastatic disease.
Time frame: From start of treatment to five years after the end of therapy. Treatment could last up to 40 weeks depending on arm, tumor response, and allowed time ranges.
Population: Eligible participants with five-year data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5-FU and Cisplatin + BID Irradiation | Number of Participants With Progression or Removal of Bladder Five Years After Therapy | 4 Participants |
| Gemcitabine + QD Irradiation | Number of Participants With Progression or Removal of Bladder Five Years After Therapy | 5 Participants |
p-value: 0.7595% CI: [0.426, 5.277]Regression, Logistic
Secondary
Number of Patients Experiencing Complete Response of the Primary Tumor After Induction Therapy
Patients will be considered as having a clinical complete response when all biopsies are negative at the site(s) of the pretreatment tumor(s).
Time frame: 3-4 weeks following induction therapy (approximately maximum 8 weeks from start of treatment depending on treatment arm and allowed time windows)
Population: Eligible patients who started induction therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5-FU and Cisplatin + BID Irradiation | Number of Patients Experiencing Complete Response of the Primary Tumor After Induction Therapy | 29 Participants |
| Gemcitabine + QD Irradiation | Number of Patients Experiencing Complete Response of the Primary Tumor After Induction Therapy | 25 Participants |
p-value: 0.395% CI: [0.129, 1.881]Regression, Logistic
Secondary
Percentage of Patients Who Completed Treatment Per Protocol
Treatment administration data was centrally reviewed to determine if patients completed each treatment component per protocol.
Time frame: After each treatment component (induction, consolidation, adjuvant). Timing varies bases on arm, tumor response at multiple time points, and allowed time ranges.
Population: Eligible patients who started each treatment component (induction, consolidation, adjuvant)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5-FU and Cisplatin + BID Irradiation | Percentage of Patients Who Completed Treatment Per Protocol | Induction Therapy | 32 Participants |
| 5-FU and Cisplatin + BID Irradiation | Percentage of Patients Who Completed Treatment Per Protocol | Consolidation Therapy | 27 Participants |
| 5-FU and Cisplatin + BID Irradiation | Percentage of Patients Who Completed Treatment Per Protocol | Adjuvant Therapy | 18 Participants |
| Gemcitabine + QD Irradiation | Percentage of Patients Who Completed Treatment Per Protocol | Induction Therapy | 31 Participants |
| Gemcitabine + QD Irradiation | Percentage of Patients Who Completed Treatment Per Protocol | Consolidation Therapy | 23 Participants |
| Gemcitabine + QD Irradiation | Percentage of Patients Who Completed Treatment Per Protocol | Adjuvant Therapy | 17 Participants |
Secondary
Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events
Highest grade adverse event (AE) per subject was counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. All adverse events are counted, regardless of reported relationship to protocol treatment.
Time frame: From start of treatment to 180 days after the end of treatment. Treatment could last up to 40 weeks depending on arm, tumor response, and allowed time ranges.
Population: Eligible patients with adverse event data for corresponding time period
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5-FU and Cisplatin + BID Irradiation | Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events | During Treatment | 19 Participants |
| 5-FU and Cisplatin + BID Irradiation | Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events | Between End of Treatment and 180 days after | 8 Participants |
| Gemcitabine + QD Irradiation | Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events | During Treatment | 18 Participants |
| Gemcitabine + QD Irradiation | Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events | Between End of Treatment and 180 days after | 5 Participants |