Adjuvant gemcitabine and concurrent continuous radiation (45 Gy) for resected pancreatic head carcinoma: a multicenter Belgian Phase II study

PURPOSE: To evaluate the feasibility and tolerance of a postoperative course of gemcitabine (GEM) combined with continuous radiation after curative resection of pancreatic adenocarcinoma. METHODS AND MATERIALS: Thirty patients (median age, 61 years; performance status, 0 to 1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. Gemcitabine 1000 mg/m2 (3 out of 4 weeks, two cycles) was given within 8 weeks of surgery and followed by GEM 300 mg/m2 weekly combined with continuous radiation (45 Gy in 25 fractions, 1.8 Gy per fraction). RESULTS: For GEM alone, all patients received the two courses with dose reductions in 14 of 30 patients (46%). All but 3 patients completed full chemoradiation; 1 stopped radiation because of subocclusion of a gastroenterostomy, and 2 did not start owing to disease progression. Reduction in GEM during radiation was necessary in 12 of 30 patients (40%). No toxic death was noted; World Health Organization Grade 3/4 hematologic and nonhematologic toxicities were seen in 10 of 30 patients (33%) and 3 of 30 patients (10%), respectively. After a median follow-up of 19 months, no late toxicity was reported. Eleven patients died from progressive disease; median disease-free survival and overall survival were 14.5 and 19 months, respectively. CONCLUSION: This adjuvant combination is well tolerated and can be safely administered after curative surgery for pancreatic cancer. Further evaluation of this regimen is ongoing.     

Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil,a randomized controlled study

PURPOSE: To determine the efficacy and tolerability of gemcitabine (GEM)-concurrent chemoradiotherapy (CCRT) vs. 5-fluorouracil (5-FU) CCRT for locally advanced pancreatic cancer. METHODS AND MATERIALS: Thirty-four patients with locally advanced pancreatic cancer were studied. Eighteen patients were randomized to receive GEM CCRT (600 mg/m(2)/wk for 6 weeks) and 16 patients to receive bolus 5-FU CCRT (500 mg/m(2)/d for 3 days repeated every 2 weeks for 6 weeks). All patients were to receive 3D-CRT 50.4-61.2 Gy at 1.8-Gy/d fractions and GEM (1000 mg/m(2) weekly for 3 weeks repeated every 4 weeks) after RT. RESULTS: The median survival and median time to progression were 14.5 months and 7.1 months for the GEM CCRT group and 6.7 months and 2.7 months for the 5-FU CCRT group (p = 0.027 and p = 0.019, respectively). The quality-adjusted life month survival time was 11.2 +/- 0.5 months for GEM CCRT and 6.0 +/- 0.3 months for 5-FU CCRT patients (p <0.001). The response rate was 50% (four complete responses and five partial responses) for GEM CCRT and 13% (two partial responses) for 5-FU CCRT (p = 0.005). Pain control was 39% for GEM CCRT and 6% for 5-FU CCRT (p = 0.043). Grade 3-4 neutropenia (34% vs. 19%), thrombocytopenia (0% vs. 7%), nausea (33% vs. 31%), vomiting (17% vs. 19%), hospitalization days per month of survival (7.4 +/- 1.7 days vs. 8.0 +/- 1.3 days), and full dose of RT received (78% vs. 75%) were not significantly different between the GEM CCRT and 5-FU CCRT patients. CONCLUSION: GEM CCRT appears more effective than 5-FU CCRT for locally advanced pancreatic cancer and has comparable tolerability.     

Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

PURPOSE: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. METHODS AND MATERIALS: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m(2)) and cisplatin (120 mg/m(2)) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. RESULTS: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. CONCLUSIONS: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.     

Long-term results with radiotherapy for stage I–II follicular lymphomas

Purpose: To analyze the long-term results with radiotherapy (RT) for early-stage, low-grade follicular lymphomas.

Methods and Materials: From 1960 to 1988, 80 patients with Stage I (n = 33) or II (n = 47), World Health Organization Grade 1 (n = 50) or 2 (n = 30) follicular lymphoma were treated with RT. The lymph nodes or spleen were involved in 97% of cases. The maximal tumor sizes ranged from 0.5 to 11.0 cm (median 2.0). The RT fields encompassed only the involved Ann Arbor nodal region (involved-field RT) in 9% of the patients. The fields also included 1–3 adjacent, grossly uninvolved nodal regions (regional RT) in 54% of patients but were smaller than mantle or whole abdominopelvic fields. Mantle or whole abdominopelvic fields encompassing up to 6 grossly uninvolved regions (extended-field RT) were used in the remaining 37% of patients. The total RT doses ranged from 26.2 to 50.0 Gy given in daily 1.0–3.0-Gy fractions.

Results: The follow-up of the surviving patients ranged from 3.5 to 28.7 years (median 19.0). No recurrences were found >17.0 years after RT, with 13 patients free of disease at their last follow-up visit 17.6–25.0 years after treatment. In 58% of cases, death was not from follicular lymphoma. The 15-year local control rate was 100% for 44 lymphomas <3.0 cm treated with only 27.8–30.8 Gy (median 30.0 in 20 fractions). Progression-free survival was affected by the maximal tumor size at the start of RT (15-year rate 49% vs. 29% for lymphomas <3.0 cm vs. ≥3.0 cm, respectively, p = 0.04) and Ann Arbor stage (15-year rate 66% vs. 26% for Stages I and II, respectively, p = 0.006). Ann Arbor stage also affected the cause-specific survival (15-year rate 87% vs. 54% for Stages I and II, respectively, p = 0.01). No significant difference was found in overall survival between those treated with extended-field RT and those treated with involved-field RT or regional RT (15-year rate 49% and 40%, respectively, p = 0.51). The 15-year incidence rate of Grade 3 or greater late complications according to the Subjective, Objective, Management, and Analytical scale in patients treated with 26.2–30.8 Gy vs. 30.9–50.0 Gy was 0% and 6%, respectively.

Conclusions: RT can cure approximately one half of Stage I and one quarter of Stage II, World Health Organization Grade 1 or 2 follicular lymphomas. Follicular lymphomas <3.0 cm can be controlled locally with doses of 27.8–30.8 Gy, and there is a trend toward a higher incidence of late complications with doses of >30.8 Gy. Doses of 25–30 Gy delivered in 15–20 fractions should be examined prospectively in patients with follicular lymphomas of <3.0 cm.     

Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results

PURPOSE: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >/=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.     

Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer: an update of the Dutch Deep Hyperthermia Trial

PURPOSE: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. METHODS AND MATERIALS: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT+HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. RESULTS: At the 12-year follow-up, local control remained better in the RT+HT group (37% vs. 56%; p=0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT+HT; p=0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. CONCLUSIONS: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.     

Preliminary analysis of RTOG 9708: Adjuvant postoperative radiotherapy combined with cisplatin/paclitaxel chemotherapy after surgery for patients with high-risk endometrial cancer

PURPOSE: Patients with completely resected high-risk endometrial cancer have a risk of disease recurrence even with the addition of adjuvant pelvic radiotherapy (RT). A Phase II study was completed by the Radiation Therapy Oncology Group to assess the safety and toxicity of chemotherapy when combined with pelvic RT for these patients. METHODS AND MATERIALS: Eligibility requirements included a total abdominal hysterectomy and bilateral salpingo-oophorectomy with Grade 2 or 3 endometrial adenocarcinoma with >50% myometrial invasion, stromal invasion of the cervix, or pelvic-confined extrauterine disease. This study was designed to administer 4500 cGy in 25 fractions to the pelvis, along with cisplatin (50 mg/m(2)) on Days 1 and 28. Vaginal brachytherapy with a low-dose-rate applicator (1 x 20 Gy to the surface) or high-dose-rate applicator (3 x 6 Gy to the surface) was performed after external beam RT. Four courses of cisplatin (50 mg/m(2)) and paclitaxel (175 mg/m(2)) were given at 4-week intervals after RT completion. RESULTS: Forty-six patients were entered between October 1997 and April 1999. Two patients were ineligible (one with previous bladder cancer and one who had undergone surgery >8 weeks before the start of RT). Follow-up ranged from 6.9 to 48.8 months (median, 28.7 months). The disease was Stage III, II, and I in 66%, 16%, and 18% of patients, respectively. Two patients were not assessable because of incomplete treatment data. The protocol completion rate was 98% (41 of 42 assessable patients). Acute toxicity during RT/chemotherapy was Grade 1 in 27%, Grade 2 in 43%, Grade 3 in 27%, and Grade 4 in 2%. During adjuvant chemotherapy, the toxicity was Grade 1 in 7%, Grade 2 in 7%, Grade 3 in 21%, and Grade 4 in 62%. Severe toxicity was primarily hematologic. Chronic toxicity was Grade 1 in 20%, Grade 2 in 39%, Grade 3 in 16%, and Grade 4 in 2%, including 1 patient with a Grade 4 small bowel complication. At 24 months, the pelvic recurrence, regional recurrence, distant recurrence, disease-free survival, and overall survival rate was 2%, 3%, 17%, 83%, and 90%, respectively. CONCLUSION: This treatment protocol demonstrated an excellent treatment completion rate and expected toxicity. Longer follow-up is needed to assess the outcome. To assess the efficacy of this adjuvant treatment program, a Phase III trial (Radiation Therapy Oncology Group 9905) was designed with high-risk uterine-confined disease to be randomized between pelvic RT alone and pelvic RT with chemotherapy.     

Gemcitabine versus combined chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer

Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced pancreatic cancer, but there is no established second-line treatment after GEM failure. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32 patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy and GEM, respectively. The median survival time in the FP therapy and GEM was 137 days and 241 days, respectively. Although clinical benefit was similar in both types of therapy, median survival time was more favorable for GEM, especially for Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP therapy group. Our data indicate that FP therapy is not considered to be a useful second-line agent in patients with GEM pretreated pancreatic cancer.     

Definitive results of a phase II trial of cisplatin, epirubicin, continuous-infusion fluorouracil, and gemcitabine in stage IV pancreatic adenocarcinoma.

PURPOSE: To evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients < or = 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status < or = 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m2/d as a protracted venous infusion. RESULTS: Between April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients. CONCLUSION: PEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.     

Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer

Purpose: To assess the toxicity and efficacy of preoperative chemoradiation in pancreatic cancer.

Methods and Materials: Between November 1996 and December 2001, 32 patients with biopsy-proven pancreatic adenocarcinoma (28 head; 4 body) were treated by chemoradiation consisting of either split-course therapy (two courses of 15 Gy separated by a 2-week break, n = 10) or standard-fractionation therapy (45 Gy during 5 weeks, n = 22). Concurrent chemotherapy included continuous infusion of 5-fluorouracil and a cisplatin bolus. Pancreatic resection was scheduled for 4–6 weeks after completion of chemoradiation treatment.

Results: All 32 patients completed the chemoradiation protocol. Only 2 cases of Grade 3 toxicity (weight loss, vomiting) and one fatal Grade 4 infection occurred. Of the 32 patients, 19 underwent curative resection. Two patients had a complete pathologic response. One patient died 36 months after diagnosis of late treatment-related toxicity (acute superior mesenteric artery thrombosis) with no evidence of disease. The 2-year overall survival rate for the entire group and the resected patients was 37.3% (95% confidence interval 18.2–56.4%) and 59.3% (95% confidence interval 34.1–84.9%), respectively.

Conclusion: Preoperative chemoradiation with 5-fluorouracil and cisplatin is feasible and promising.     

Feasibility and anti-tumor activity of postoperative adjuvant chemotherapy with gemcitabine for resected pancreatic cancer

The feasibility and anti-tumor activity of gemcitabine (GEM) as postoperative adjuvant chemotherapy were evaluated retrospectively. Between September 1998 and June 2007, patients with resected invasive pancreatic cancer (stage III, IVa, IVb) were given adjuvant chemotherapy with GEM (GEM group, n=10) or did not receive chemotherapy (n=11). Started the administration of GEM 38.5 days after surgery, and the mean duration was 15.4 months. Grade 3 or 4 adverse event was not observed in the GEM group. There was a significant difference in overall survival between the GEM group and the no-chemotherapy group (p=0.037), but there was no significant difference in disease-free survival between the two groups. Adjuvant chemotherapy with GEM was feasible and showed a benefit in patients with invasive pancreatic cancer.     

Phase II trial of up-front accelerated thoracic radiotherapy combined with chemotherapy and optional up-front prophylactic cranial irradiation in limited small-cell lung cancer. Groupe d'Oncologie Thoracique des Régions Alpines.

PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m(2) for 3 days and cisplatin 25 mg/m(2) for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m(2) dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.     

Phase III trial comparing intensive induction chemoradiotherapy (60 Gy,infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000–01 FFCD/SFRO study

BackgroundThe role of chemoradiation with systemic chemotherapy compared with chemotherapy alone in locally advanced pancreatic cancer (LAPC) is uncertain.Patients and methodsOne hundred and nineteen patients with LAPC, World Health Organization performance status of zero to two were randomly assigned to either the induction CHRT group (60 Gy, 2 Gy/fraction; concomitant 5-fluorouracil infusion, 300 mg/m²/day, days 1–5 for 6 weeks; cisplatin, 20 mg/m²/day, days 1–5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m² weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m² weekly, 3/4 weeks) was given in both arms until disease progression or toxicity.ResultsOverall survival was shorter in the CHRT than in GEM arm [median survival 8.6 (99% confidence interval 7.1–11.4) and 13 months (8.7–18.1), P = 0.03]. One-year survival was, respectively, 32% and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3–4 toxic effects were recorded in the CHRT arm, both during induction (36 versus 22%) and maintenance (32 versus 18%).ConclusionThis intensive induction schedule of CHRT was more toxic and less effective than gemcitabine alone.     

Weekly gemcitabine and 24-hour infusional 5-fluorouracil in advanced pancreatic cancer: a phase I-II study

OBJECTIVE: In this phase I-II study we explored the potential of the combination of weekly gemcitabine (GEM) and 24-hour continuous infusion of 5-fluorouracil (5-FU) in order to determine the toxicity profile in pancreatic cancer. The efficacy of this drug combination was studied as a secondary endpoint. METHODS: Twenty-one patients with histologically or cytologically proven unresectable or metastatic previously untreated pancreatic adenocarcinoma were included in this study. Two dose levels of GEM and two dose levels of 5-FU were evaluated in three cohorts of patients who received GEM 1,000 mg/m(2) and 5-FU 2,000 mg/m(2), GEM 1,200 mg/m(2) and 5-FU 2,000 mg/m(2), or GEM 1,200 mg/m(2) and 5-FU 2,250 mg/m(2), on days 1, 8, and 15, every 4 weeks, respectively. RESULTS: Grade 3-4 neutropenia was observed in 10% of the cycles. Non-myelosuppressive toxicities included fatigue (22%), grade 1-2 diarrhea (12%) and grade 1 liver toxicity. There was no limiting toxicity and the maximum tolerated dose has not been reached. Two patients experienced a partial response (9.5 +/- 12.6%) and 12 patients had stable disease (57.1 +/- 21.2%). Seven of the 14 symptomatic patients improved their disease-related symptoms and 4 of the 8 patients evaluable for clinical benefit had a clinically beneficial response (50 +/- 34.6%). The median progression-free survival was 6 months (range 2-28), median survival was 11 months (range 3-32+), and the actuarial 1-year survival rate 33%. CONCLUSION: The weekly administration of GEM combined with 24-hour continuous infusion of 5-FU shows a good safety profile at the dose levels evaluated. Some partial responses had also been achieved, disregarding the dose level of the two drugs. Survival confirms the activity of this drug combination.     

Paclitaxel and concurrent radiation for locally advanced pancreatic cancer

Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer.

Methods and Materials: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m² by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments.

Results: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%.

Conclusion: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.     

Adjuvant radiotherapy and concomitant 5-fluorouracil by protracted venous infusion for resected pancreatic cancer

Purpose: To assess the toxicity and clinical benefit from adjuvant chemoradiotherapy consisting of protracted venous infusion 5-fluorouracil (5-FU) and concomitant radiotherapy in patients with resected pancreatic cancer.

Methods and Materials: Between 1994 and 1999, 52 patients who underwent pancreaticoduodenectomy received adjuvant chemoradiotherapy. The tumor bed and regional nodes received a dose of 45 Gy in fractions of 1.8 Gy followed by boost to the tumor bed if the surgical margins were involved (total dose, 54 Gy). The patients also received concomitant 5-FU by protracted venous infusion (200–250 mg/m²/day, 7 days/week) during the entire radiotherapy course.

Results: Fifty-two patients (30 men, 22 women) were enrolled and treated on this protocol. The median age was 63 years (range, 38–78 years), and the median Karnofsky Performance Status was 80 (range, 70–100). Thirty-five percent had involved surgical margins and 59% had involved lymph nodes. All patients completed therapy, and there were no Grade IV/V toxicities observed. With median follow-up of 24 months (range, 3–52 months) for surviving patients, the median survival is 32 months, and 2-year and 3-year survivals are 62%, and 39%, respectively.

Conclusion: Radiotherapy with concomitant 5-FU by protracted venous infusion as adjuvant treatment for resected pancreatic cancer is well tolerated. This approach allows for greater dose intensity with reduced toxicity. The median survival of this cohort of patients compares favorably with our earlier experience and other published series.     

Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy

PURPOSE: To report the incidence of late complications in long-term survivors of very-high-dose thoracic radiotherapy (RT) treated on a prospective clinical trial. METHODS AND MATERIALS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved lymph nodes to a dose of 73.6 Gy at 1.6 Gy twice daily. If the plasma transforming growth factor-beta1 (TGF-beta1) level was normal after 73.6 Gy, additional twice-daily RT was delivered to successively higher total doses until the maximal tolerated dose was reached. Patients within a given dose level were followed for 6 months before escalation to the next dose level was permitted. Late complications were defined according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Thirty-eight patients were enrolled between 1996 and 1999. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF-beta1 levels. Fourteen patients received dose escalation (80 Gy in 8; 86.4 Gy in 6). Grade 3 or greater late complications occurred in 4 of 24, 1 of 8, and 2 of 6 patients treated to 73.6, 80, and 86.4 Gy, respectively. The corresponding patient numbers with late Grade 4-5 toxicity were 3 of 24, 0 of 6, and 0 of 8. Overall, 7 (18%) of the 38 patients developed Grade 3-5 late toxicity. Nonpulmonary complications predominated (4 of 7). Five (71%) of seven serious complications developed within 11 months after RT; however, the remaining two complications (29%) occurred very late (at 43 and 62 months). The 5-year actuarial risk of late Grade 3-5 complications was 33%. CONCLUSION: Long-term survivors of very-high-dose RT for non-small-cell lung cancer have a significant risk of severe treatment-related complications. At these high dose levels, the predominant toxicity may no longer be pulmonary. All Grade 4-5 complications occurred in patients whose dose was limited to 73.6 Gy because of a persistently elevated TGF-beta1. Thus, persistently elevated plasma TGF-beta1 levels toward the end of RT may identify patients at greatest risk of severe complications.     

吉西他滨为基础的化疗方案治疗进展期胰腺癌的临床研究

背景与目的:进展期胰腺癌预后差.吉西他滨可以改善胰腺癌患者的生存质量,但吉西他滨联合方案疗效是否优于单药,还存在争议,国内更缺乏相关的临床研究.本研究目的是比较吉西他滨为基础的联合化疗方案与吉西他滨单药治疗进展期胰腺癌的疗效.方法:回顾性分析2000～2005年收治的40例经临床或病理确诊的进展期胰腺癌临床资料,其中吉西他滨单药组15例,吉西他滨剂量为1 000 mg/m2,每周1次,连用7周,休息2周,之后每周1次,连用3周,4周重复;吉西他滨联合治疗组25例,联合化疗方案包括吉西他滨1 000 mg/m2,每周1次,连用2周,分别联合:(1)氟尿嘧啶425～600 mg/m2,静脉滴注或持续静脉泵入,d1-5,3周重复;(2)顺铂60～75 mg/m2,分第1、2天,3周重复;(3)奥沙利铂85～130 mg/m2,d1,3周重复;(4)卡培他滨l000 mg/m2,2次/天,d1-14,3周重复.采用Kaplan-Meier生存曲线分析患者的生存期,并比较两组间的临床受益反应、中位疾病进展时间、中位生存时间和不良反应.结果:吉西他滨联合组与单药组患者的临床受益反应均得到改善(56.0% vs.46.7%),但疾病控制率、中位生存时间、临床受益反应在两组之间差异无统计学意义(P＞0.05),不良反应的发生率也相似(P＞0.05).对Ⅲ～Ⅳ期患者进行分层分析,发现吉西他滨联合组疾病控制率高于单药组(75.0% vs.45.5%),但无统计学意义(P=0.13).结论:吉西他滨联合方案与单药治疗进展期胰腺癌相比,疗效、临床受益反应、中位生存时间两组相似.     

Late effects of radiotherapy for pediatric extremity sarcomas

PURPOSE: To determine the long-term effects of radiotherapy (RT) in children treated for extremity sarcoma. PATIENTS AND METHODS: Between 1964 and 1997, 15 of 33 children treated with RT for extremity sarcomas at the University of Iowa have survived with a median follow-up was 20 years (range, 6-36 years). There were 10 boys and 5 girls with a median age of 13 years (range, 3.5-20 years) at the time of irradiation. The diagnosis was Ewing's sarcoma in 8 (53%), synovial sarcoma in 4 (27%), alveolar rhabdomyosarcoma in 2, and fibrosarcoma in 1. Location of primary tumor was lower extremity in 10 (67%) and upper extremity in 5 (33%). RT was given as the definitive therapy for 9 children (median dose, 55.8 Gy; range, 45-66 Gy) and as an adjuvant postoperative treatment in 6 (median, 63 Gy; range, 41.4-66.4 Gy). (60)Co was used in 6 (40%), 4 mV in 4, 6 mV in 2, and 250 kV photons in 2 patients; 1 child was treated with a combination of 12 and 15 MeV electrons for a Ewing's sarcoma of the distal femur. Another child had a 25 Gy intraoperative RT boost after 41.4 Gy conventional RT. Late effects to the muscle, soft tissue, and growing bone were assessed using the objective portion of the LENT-SOMA scale proposed by the Late Effects Consensus Conference. RESULTS: Late effects were seen in all patients and included atrophy in 12 (80%), fibrosis in 12 (80%), bone growth abnormalities in 10 (67%), impairment of mobility and extremity function in 6 (40%), edema in 3 (20%), and peripheral nerve injury in 2 (13%). Ten of 15 (67%) children had Grade 1 or 2 growing bone, muscle, soft tissue, or peripheral nerve complications. Two patients (13%) had a Grade 3 mobility and extremity function score and had moderate to severe limitation of movement. Two children (13%) required epiphysiodesis because of a shorter treated leg. The patient who received an intraoperative RT boost of 25 Gy developed sensory dysfunction of the ulnar nerve 11 years after RT. Another developed radial nerve palsy 3 years after marginal resection and postoperative RT and required tendon transfer repair. One patient had radiation-induced vasculitis with popliteal artery thrombosis 23 years after RT. Five (33%) developed a fracture of the irradiated bone at a median time of 8 years after RT (range: 9 months to 22.2 years); all had Ewing's sarcoma, and 3 of these patients were subsequently found to have a secondary bone cancer (osteosarcoma 2, malignant fibrous histiocytoma 1) in the RT field. One of these patients also developed breast cancer 26 years after lung RT for metastatic Ewing's sarcoma. Overall, 11 surgical procedures in 8 children were performed to correct a limb preservation treatment toxicity. CONCLUSIONS: Although most children treated with RT for a pediatric extremity sarcoma have minimal late toxicity by LENT-SOMA scale, approximately half required a surgical procedure to correct a late effect. A fracture in the irradiated bone may be the presenting sign or may precede a radiation-induced bone malignancy, as seen in 3 of the patients in this study.     

Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial

PURPOSE: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. METHODS AND MATERIALS: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. RESULTS: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located < or = 6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). CONCLUSION: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a basis for additional investigation regarding RT dose escalation or the addition of concomitant chemotherapy.