Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: a longitudinal prospective study. Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study. Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer. [Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer]. Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.
Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC.
                Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS).
                Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016).
                Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages. To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC).
                Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B.
                Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009).
                An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome. Between January 1988 and December 1991, 159 patients with Stage III/IV (M0) squamous cell carcinoma of the head and neck were randomized to receive standard fraction RT (70 Gy) (group I) or the same RT plus either 6 mg/m2 of cisplatin (CDPP) (group II) or 25 mg/ m2 of carboplatin (CBDCA) both given daily during RT (group III). Patients in groups II and III had significantly higher overall response rates then those in group I (P = 0.011 and P = 0.0025, respectively) with no difference between groups II and III (P = 0.60). They also had significantly longer median survival time (MST) and higher 5-year survival rates than those in group I (MST, 32 months (32%) and 30 months (29%) versus 16 months (15%), respectively; P = 0.011 and P = 0.019, respectively), with no difference between the two RT/CHT groups. Median time to local recurrence (MTLR) and 5-year local recurrence-free survival (LRFS) were significantly higher for both RT/CHT when compared to RT alone (MTLR, not attained yet and 30 months versus 10 months, respectively; 5-year LRFS, 51% and 48% versus 27%, respectively; P = 0.018 and P = 0.040, respectively) with no difference between the two RT/CHT groups. There was no difference between the three treatment groups regarding regional lymph node and distant metastasis control. Apart from acute high grade (> or =3) hematological toxicity that was significantly more frequent in the two RT/CHT groups and no different between the two RT/CHT groups, other acute high grade toxicity was similar between the three treatment groups. Late high grade toxicity was infrequent and similar between the three treatment groups. To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer.
                We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses.
                Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas.
                One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised. Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone.
                Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT.
                A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms.
                Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility. In a prospective randomized study, 434 mHz microwave therapy combined with external beam radiotherapy (VHF + RT) was compared with standard external beam radiotherapy (RT) in controlling locally recurrent or unresectable primary adenocarcinoma of the rectum. Independent assessors documented quality of life scores, performance status, toxicities, local response to treatment, and systemic disease progression before treatment and after treatment and every 8 weeks thereafter. Of 75 patients randomized, 73 were eligible for inclusion in the study. Forty-three of these patients had local pelvic tumour recurrence only and 21 also had distant metastases. In addition, nine patients had primary inoperable carcinomas, two of whom also had metastases. Thirty-seven patients were randomized to RT and 36 to VHF + RT. The median dose of radiation in the VHF+RT arm was 4275 cGy with a median fraction size of 150 cGy and median duration of therapy of 48.5 days versus 4500 cGy in the RT-only arm with a median fraction size of 180 cGy and median duration of therapy of 38 days. These doses are unlikely to be significantly different in biological effect. No significant difference between the two groups was observed in extent and duration of local control, measures of toxicity or quality of life scores. Additionally, survival and cumulative incidence of pelvic site of first progression did not differ significantly between the groups. We conclude that VHF microwave therapy in conjunction with radiotherapy produces no therapeutic advantage over conventional radiation therapy alone in the treatment of locally recurrent rectal carcinoma. A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them. A population based prospective randomized trial on preoperative radiotherapy in operable rectal cancer was conducted in Stockholm, Sweden. Five hundred fifty-seven patients from 12 institutions were included with histologically proven, clinically resectable rectal adenocarcinoma. Patients planned for local excision or previously irradiated to the pelvis were excluded.
                A total of 272 patients were allocated to preoperative irradiation with 25 Gy in five cycles during 5-7 days to the rectum and the pararectal tissues (RT+ group) and 285 patients were allocated to surgery only (RT- group). The median follow-up time was 50 months. No patient was lost to follow-up. Surgery was considered curative in 479 patients (86%).
                Locoregional recurrence occurred in 10% of the patients in the RT+ group versus 21% in the RT- group (p < 0.01). Among the curatively operated patients, distant metastases occurred in 19% in the RT+ group versus 26% in the RT- group (p = 0.02). The overall survival was improved in the irradiated patients (p = 0.02). Postoperative complications were more common after irradiation but were usually mild. The postoperative mortality was low in both groups.
                Preoperative short-term, high-dose radiotherapy as given in this trial reduces the risk of local and distant recurrence and improves survival after curative surgery for rectal carcinoma. To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma.
                Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT.
                Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group.
                The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.
RT was compared to the more intensive CRT in the treatment of T3-4, node positive (locally advanced) rectal cancer. While there was no difference in overall survival between RT and CRT, CRT was associated with less local recurrence.