Twice-daily Radiotherapy Research Articles

Patient Preferences and Physician Practice Patterns Regarding Breast Radiotherapy

Patient Preferences and Physician Practice Patterns Regarding Breast Radiotherapy

CONVERT: Concurrent once-daily versus twice-daily radiotherapy – a new phase III randomised controlled trial for patients with limited-stage small cell lung cancer and good performance status

CONVERT: Concurrent once-daily versus twice-daily radiotherapy – a new phase III randomised controlled trial for patients with limited-stage small cell lung cancer and good performance status

Phase I-II RTOG Study (99-06) of Patients With Muscle-Invasive Bladder Cancer Undergoing Transurethral Surgery, Paclitaxel, Cisplatin, and Twice-daily Radiotherapy Followed by Selective Bladder Preservation or Radical Cystectomy and Adjuvant Chemotherapy

To evaluate the safety, tolerance, protocol completion rate, tumor response rate, and patient survival of chemoradiotherapy for patients with muscle-invasive operable bladder cancer. After transurethral resection of the tumor in patients with Stage T2-T4a bladder cancer, twice-daily radiotherapy with paclitaxel and cisplatin chemotherapy induction (TCI) was administered. If repeat biopsy showed less than Stage T1 disease, consolidation with TCI was given. If repeat biopsy showed greater than Stage T1 disease, cystectomy was recommended. Adjuvant gemcitabine and cisplatin were given to all patients. A total of 80 patients met protocol eligibility. TCI resulted in 26% developing grade 3-4 acute toxicity, mainly gastrointestinal (25%). During consolidation TCI, grade 3-4 acute toxicity, all transient, was reported in 8%. Four cycles of adjuvant chemotherapy were completed per protocol or with minor deviations in 70% of the patients. Adjuvant treatment was associated with grade 3 toxicity in 46% and grade 4 in 26%. One patient had a fatal hemorrhagic stroke. Late bladder radiation toxicity was evaluated in 53 patients with > or = 2 years of follow-up. Of these 53 patients, 3 experienced self-limited, late grade 3 bladder toxicity. The postinduction complete response rate was 81% (65/80), 36 of the 80 patients died (22 of bladder cancer). At a median follow-up of 49.4 months, the actuarial 5-year overall and disease-specific survival rate was 56% and 71%, respectively. These favorable tumor response rates with possible increased bladder preservation rates suggest that this treatment regimen deserves further study.

Impact of Treatment Duration and Delays on In-field Disease Control for Twice-daily Radiotherapy (BID-RT) with Concurrent Chemotherapy in Limited-stage Small-cell Lung Cancer (SCLC)

Impact of Treatment Duration and Delays on In-field Disease Control for Twice-daily Radiotherapy (BID-RT) with Concurrent Chemotherapy in Limited-stage Small-cell Lung Cancer (SCLC)

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer

Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients. Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups. The intervention group were scheduled to receive three cycles of cisplatin and etoposide, followed by twice-daily radiation with concurrent carboplatin and vindesine, and then surgical resection (those with positive resection margins or unresectable disease were offered further twice-daily radiotherapy). The control group were scheduled to receive three cycles of cisplatin and etoposide, followed by surgery, and then further radiotherapy. The primary endpoint was median progression-free survival (PFS) in patients eligible for treatment after randomisation. Secondary endpoints in patients eligible for treatment after randomisation were overall survival (OS) and the proportion of patients undergoing surgery. Secondary endpoints in patients with tumour resection were the proportion with negative resection margins, the proportion with complete resection, the proportion with histopathological response, and the proportion with mediastinal downstaging. Additionally, exploratory (not prespecified) post-hoc analyses in terms of PFS and OS were done on patients not amenable to resection and on further subgroups of patients undergoing resection. Analyses were by intention to treat. This trial is registered on the ClinicalTrials.gov website, number NCT 00176137. 558 patients were randomly assigned. 34 patients did not meet inclusion criteria and were excluded. Of 524 eligible patients, 142 of 264 (54%) in the interventional group and 154 of 260 (59%) in the control group underwent surgery; 98 of 264 (37%) and 84 of 260 (32%) underwent complete resection. In patients with complete resection, the proportion of those with mediastinal downstaging (45 of 98 [46%] and 24 of 84 [29%], p=0.02) and pathological response (59 of 98 [60%] and 17 of 84 [20%], p<0.0001) favoured the interventional group. However, there was no difference in PFS (primary endpoint) between treatment groups-either in eligible patients (median PFS 9.5 months, range 1.0-117.0 [95% CI 8.3-11.2] vs 10.0 months, range 1.0-111.0 [8.9-11.5], 5-year PFS 16% [11-21] vs 14% [10-19], hazard ratio (HR) 0.99 [0.81-1.19], p=0.87), in those undergoing tumour resection, or in patients with complete resection. In both groups, 35% of patients undergoing surgery received a pneumonectomy (50/142 vs 54/154). In patients receiving a pneumonectomy, treatment-related mortality increased in the interventional group compared with the control group (7/50 [14%] vs 3/54 [6%]). In patients with stage III NSCLC amenable to surgery, preoperative chemoradiation in addition to chemotherapy increases pathological response and mediastinal downstaging, but does not improve survival. After induction with chemoradiation, pneumonectomy should be avoided. German Cancer Aid (Bonn, Germany).

Favorable survival observed after carboplatin, paclitaxel, and concurrent accelerated hyperfractionated radiotherapy for treatment of locally advanced head and neck carcinoma

Several trials have demonstrated the superiority of simultaneous chemoradiotherapy compared with radiation alone for patients with locally advanced head and neck cancers. However, the optimal regimen remains to be defined. This study assessed the safety and activity of combined carboplatin (C), paclitaxel (P), and twice-daily radiotherapy (RT) in a community based, multicenter, phase II trial. Eligible patients (N = 52) had ECOG PS 0-2 and previously untreated, stage III or IV (M0), unresectable, squamous cell cancers of the head and neck. Treatment consisted of 6 weekly courses of C (AUC = 1), P (40 mg/m(2)/1-h) and twice-daily radiation (120 cGy BID; total dose of 6,960 cGy). Subsequently, patients with N2/N3 disease were permitted neck dissection. Median follow-up was 61 months. Sixty-seven percent (67%) of patients had stage IV (M0) disease at baseline. Fifty-five percent (55%) of treated patients experienced NCI Grade 3-4 dysphagia, stomatitis, or mucositis; 80% had > or = Grade 3 toxicity of any organ system. Median weight loss was 7.1 lbs; 35% of patients experienced 10% or more weight loss. Of 43 patients evaluable for response, responses were: 29 CR (67%), 7 PR (16%), 1 MR (2%), 4 SD (9%), and 2 PD (5%); the overall response rate (CR+PR) was 84%. For the entire cohort of 52 patients, the estimated overall survival at 36 months was 60%; progression-free survival was 50%. We conclude that weekly C + P and concurrent twice-daily hyperfractionated radiotherapy is tolerated and highly active in patients with unresectable, locally advanced squamous cell carcinoma of the head and neck.

CONVERT: Concurrent ONce-daily VErsus twice-daily RadioTherapy. A new phase III randomised controlled trial for patients LS SCLC and good performance status

CONVERT: Concurrent ONce-daily VErsus twice-daily RadioTherapy. A new phase III randomised controlled trial for patients LS SCLC and good performance status

Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902

Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902

Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer—a Danish Oncological Lung Cancer Group (DOLG) phase II trial

The longest survival time reported in randomised trials of limited disease (LD) SCLC has been achieved with early twice-daily concurrent chemoradiation. Topotecan is active in recurrent SCLC and in extensive disease as first line treatment. To incorporate and assess the effect of topotecan with concurrent twice-daily radiochemotherapy in LD SCLC. Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1; vincristine, 1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days. Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) < or =2. Pts older than 64 years with PS=2 and LDH>two times the upper limit were excluded. Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43-75. PS was < or =1 in 90% of pts. Non-haematological toxicity was mild except grade 3 esophagitis, which was observed in 26.5% of pts. One pt developed an esophageal stricture. Grade 3/4 leucopenia and thrombocytopenia were observed in 82.5% and 75.0 of pts, respectively. One patient died due to neutropenic sepsis. The overall response rate was 77.5% with 30.0% achieving a complete response. Median progression-free survival was 11.8 months (95% CI: 1.3-22.2). Median overall survival was 22.9 months (95% CI: 13.4-31.5) and 5-year survival was 21%. The combination of topotecan and cisplatin with concurrent twice-daily chemoradiation results in long-term survivors. As expected the incidence of severe esophagitis is high.

Phase II Study of Low-Dose Paclitaxel and Cisplatin in Combination With Split-Course Concomitant Twice-Daily Reirradiation in Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of Radiation Therapy Oncology Group Protocol 9911

Recurrent squamous cell carcinoma of the head and neck (SCCHN) or new second primary tumor (SPT) in a previous radiation field, if not curable by surgery or radiation, is almost always fatal. Chemotherapy alone yields a median survival time (MST) of no more than 10 months and 1-year overall survival (OS) of 35% at best. Concurrent reirradiation and chemotherapy is an alternative strategy. Eligibility for Radiation Therapy Oncology Group (RTOG) protocol 9911 stipulated recurrent SCCHN or SPT in a previous radiation field. Patients received twice-daily radiation (1.5 Gy per fraction bid x 5 days every 2 weeks x4), plus cisplatin 15 mg/m2 intravenously (IV) daily x 5 and paclitaxel 20 mg/m2 IV daily x 5 every 2 weeks x4. Granulocyte colony-stimulated factor was administered days 6 through 13 of each 2-week cycle. One hundred five patients were enrolled from March 2000 through June 2003; 23% had SPT. Oropharynx (40%) and oral cavity (27%) were the predominant primary sites. Median prior radiation dose was 65.4 Gy. Seventy-four percent of patients completed chemotherapy. Grade 4 or worse acute toxicity occurred in 28%, grade 4 or worse acute hematologic toxicity in 21%. Eight treatment-related deaths (8%) occurred: five in the acute setting, three late (including two carotid hemorrhages). MST was 12.1 months, with estimated 1- and 2-year OS rates of 50.2% and 25.9%. Despite a high incidence of grade 5 toxicity, 1- and 2-year OS rates for split-course bid radiation therapy and concurrent cisplatin/paclitaxel exceed results generally seen with chemotherapy alone.

The progress of small cell lung cancer management using irinotecan plus cisplatin chemotherapy

7721 Background: Etoposide/cisplatin (EP) is the most widely used regimen resulting in a median survival of 8–10 mos and 17–20 mos respectively for patients (pts) with extensive-disease (ED) and limited-disease (LD). Encouraged by a phase III trial result that showed better survival outcome after Irinotecan/cisplatin (IP) combination as compared with EP, we previously reported promising activity of IP regimen for LD-SCLC and also for ED-SCLC. To further evaluate the role of IP in SCLC pts, we conducted two additional phase II studies. Methods: Between May 2003 and June 2006, a total of 196 SCLC pts (ED: 120, LD: 76) were enrolled in two separate trials. All pts were chemo-naive and ECOG PS of 0–2. Pts with ED-SCLC received irinotecan 60 mg/m2 intravenously (IV) and cisplatin 30 mg/m2 IV on days 1 and 8 every 21 days for 8 cycles followed by 6 cycles of irinotecan maintenance or observation. Treatment for LD-SCLC consisted of two 28-day cycles of cisplatin 30 mg/m2 IV on days 1 and 8 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15, followed by two 21-day cycles of cisplatin 60 mg/m2 IV on day 1, plus etoposide 100 mg/m2 IV on days 1 to 3 with concurrent twice-daily thoracic radiation of total 45 Gy. Hoping to modify the treatment-related toxicity, 36 pts were given epoietin and 20 were given amifostine while 15 received neither during the concurrent chemo-radiation therapy. Results: For ED- SCLC, overall response rate was 92.6% with CR rate of 11.1%. The median survival was 13.8 mos (95% CI, 12.2 to15.3) with 1-and 2-year survival rates of 58.6% and 18.9%. The median progression-free survival (PFS) was 7.3 mos with 1-and 2-year PFS rates of 18.1% and 5.4%. Irinotecan maintenance did not affect the outcome, however. For LD-SCLC, the response rate was 97.1% with CR rate of 44.9%. The median survival was 24.9 mos (95% CI, 18.5 to 31.3) with 1-and 2-year survival rates of 75.2% and 51.4%. The median PFS was 11.0 mos (95% CI, 7.8–14.2) with 1-year PFS rates of 46.8%. The most common toxicity associated with IP treatment was grade 3 or 4 neutropenia (64.6% for ED, 45.3% for LD). Grade 3 diarrhea was developed in 12.4% for ED and 4% for LD pts. Conclusion: Significant antitumor activity of IP chemotherapy as shown suggests further progress in SCLC therapy. No significant financial relationships to disclose.

Therapeutic outcomes of laryngeal cancer at Kyoto University Hospital for 10 years

Conclusion: It is important to prevent regional lymph node recurrence and distant metastasis to achieve better survival of laryngeal cancer. Objective: Therapeutic outcomes of 130 cases with laryngeal cancer treated at Kyoto University Hospital between 1995 and 2004 were reviewed. Patients and methods: In all, 121 males and 9 females were involved. Their ages ranged from 40 years to 92 years (average 66 years). All tumors were squamous cell carcinoma – arising at the glottis in 111 cases, the supraglottis in 18, and the subglottis in 1 case. Most glottic cancers (77.5%) were classified as stage I or II, while most supraglottic cancers (77.8%) were at stage III or IV. Stage I/II cancers were basically treated by conventional radiotherapy (60–66 Gy) and twice-daily hyperfractionated radiotherapy (70–74 Gy), respectively, attempting to preserve the larynx. Total laryngectomy with neck dissection was performed in the treatment of stage III/IV cases. Results: Five-year disease-specific survival rates were 100%, 96%, 100%, and 68% for stage I, II, III, and IV, respectively. Five-year laryngeal preservation rates were 98%, 100%, 86%, 0%, and 0% for T1a, T1b, T2, T3, and T4 of glottic cancer, respectively. Local recurrence occurred in five cases of stage I/II glottic cancer, which was successfully salvaged. Regional lymph node recurrence occurred in five cases including four patients with glottic cancer and one with supraglottic cancer. Two of them died of disease despite undergoing salvage therapy. Distant metastasis occurred in the lung in four cases including one glottic and three supraglottic cancer patients after initial treatment.

Final results of a Phase I/II dose escalation trial in non–small-cell lung cancer using three-dimensional conformal radiotherapy

The aim of this study was to determine the maximum tolerated dose (MTD) delivered within 6 weeks in patients with non-small-cell lung cancer (NSCLC). The impact of tumor volume and delivered dose on failure-free interval (FFI) and overall survival (OS) were also studied. A Phase I/II trial was performed including inoperable NSCLC patients. According to the relative mean lung dose (rMLD), five risk groups with different starting doses were defined: Group 1, rMLD 0.0 to 0.12; Group 2, rMLD 0.12 to 0.18; Group 3, rMLD 0.18 to 0.24; Group 4, rMLD 0.24 to 0.31; and Group 5, rMLD 0.31 to 0.40. Patients underwent irradiation with 2.25 Gy per fraction and a fixed overall treatment time of 6 weeks. The dose was escalated with 6.75 Gy after 6 months follow-up without dose-limiting toxicity. If more than 30 fractions were prescribed, twice-daily irradiation was performed with at least a 6-h interval. A total of 88 patients were included. Tumor Stage I or II was found in 53%, IIIA in 31%, and IIIB in 17%. The MTD was not achieved in risk Group 1 (reached dose, 94.5 Gy). For risk Groups 2 and 3 the MTD was 81 Gy. The 74.3-Gy dose was determined to be safe for Group 4 and the 60.8-Gy dose for Group 5. In 2 patients (5%) an isolated nodal relapse occurred. Based on multivariable analysis, higher doses significantly increased the FFI (p = 0.02) for the total group. The OS was increased in the lower risk groups (p = 0.05) but not in the higher risk groups (p = 0.4). Dose escalation is safe up to 94.5 Gy in 42 fractions in 6 weeks in patients with an MLD 13.6 Gy or less. Higher doses are associated with a better FFI and OS for smaller tumor volumes. Involved-field irradiation results in a low percentage of isolated nodal relapses.

Factors affecting the risk of brain metastases after chemoradiotherapy for locally advanced non-small-cell lung cancer (LA-NSCLC)

17019 Background: With an improvement in treatment outcome in patients with LA-NSCLC undergoing radical chemoradiotherapy, brain metastasis has become a greater problem. We assessed the cumulative incidence of brain metastases and its risk factors in such patients with LA-NSCLC. Methods: Between 1993 and 2003, 85 consecutive patients with stage IIIA or IIIB NSCLC underwent chemoradiotherapy in our institution. The characteristics of these patients were as follows: median age, 64 years (range, 39 to 74 years); stage IIIA/IIIB, 30/55 patients; squamous-cell/nonsquamous-cell histologies, 39/46 patients. Concurrent and sequential chemoradiotherapy were administered for 78 and 7 patients, respectively. Only two patients underwent surgical resection after chemoradiotherapy. Fifty-seven patients received conventional thoracic radiotherapy with a total dose of 59.5 ± 1.4 Gy (range, 40 to 70 Gy), and 28 received twice-daily radiotherapy with a total dose of 71.5 ± 6.5 Gy (range, 43 to 86 Gy). Thirty-eight patients received a combination chemotherapy consisting of cisplatin and docetaxel, and the remaining 47 received the other platinum-based regimens. Results: At a median follow-up time of 51 months (range, 9 to 131 months), median survival time was 25 months, with a 3-year survival rate of 36.9%. The median disease-free survival time was 13 months. During treatment and observation periods, 21 (24.7%) patients had developed brain metastases. Thirteen (15.3%) patients experienced brain metastases as the first site of relapse, and in nine (10.6%), brain was the sole site of relapse. The cumulative risk of brain metastases was 15.4% at 1-year, 21.1% at 2-year, and 25.7% at 3-year, respectively. In a multivariate analysis using Cox proportional hazard model, T-factor (T4 vs. T1–3) was the most predictive of brain failure (hazard ratio, 3.51; 95% confidence interval, 1.35 to 9.13; p = 0.01). Conclusions: In patients with LA-NSCLC undergoing chemoradiotherapy, brain was one of the most common sites of failure when locoregional control was achieved. Although efficacy of prophylactic cranial irradiation (PCI) on survival remains unclear for such patients with NSCLC, identification of patients more likely to have a benefit from PCI would be useful. No significant financial relationships to disclose.

Risk factors for hypopharyngeal/upper esophageal stricture formation after concurrent chemoradiation

Concurrent chemoradiation therapy has been demonstrated to be effective as an organ-sparing treatment for select advanced head and neck squamous cell carcinoma (HNSCC). However, this treatment modality is not without side effects. One side effect is the formation of upper esophageal strictures. As concurrent chemoradiation treatment is used more frequently, it is important to identify risk factors associated with stricture formation. A retrospective chart review of all patients who had undergone definitive concurrent chemoradiation treatment between 1989 and 2002 was performed. Exclusion criteria included death within 1 year or persistent/recurrent disease that required surgical salvage at the primary site. The outcome measure was stricture formation as determined by both objective findings (barium swallow or endoscopy) and the need for dilation after treatment. Of the 222 patients in this cohort, there were enough data for 199 patients to assess for stricture formation. Strictures developed in a total of 41 patients (21%). Significant predictive factors were a twice-daily (BID) radiation fractionation (p = .007), female sex (p = .015), and a hypopharyngeal primary site (p = .01). Age and tumor extent were not significant factors in stricture formation (p = .15 and p = .23, respectively). Symptomatic strictures occur in 21% of patients undergoing concurrent chemoradiation for HNSCC. Female sex, BID radiation fractionation, and a hypopharyngeal primary site are significant predictive factors for stricture formation.

Outcome of hyperfractionated radiotherapy in chemotherapy-resistant non-Hodgkin’s lymphoma

Patients with chemotherapy-resistant lymphoma have rapidly progressive disease and a poor prognosis. Local symptoms are treated with radiotherapy (RT) for local control. We have reviewed local control and toxicity in patients treated with hyperfractionated accelerated RT. A total of 34 patients received hyperfractionated RT between 1997 and 2003. The radiation dose was 39.9-40.5 Gy in 30 fractions. The median treatment time was 22 days with twice-daily involved-field RT. The median follow-up was 4.4 years. Response was assessed <3 months after RT and was classified as a complete response, a complete response-unconfirmed, a partial response, or no response. Local control was defined as maintenance of local complete response, complete response-unconfirmed, or lack of local progression with a partial response. Recurrence or progression outside the RT volume was regarded as distant disease. The median age was 53 years; 20 patients were men and 14 were women. The initial diagnosis was Stage I-II in 56% and Stage III-IV in 44%. The disease bulk was > or =10 cm in 35% (n = 12). The histologic features at diagnosis were follicular in 11 (Grade 1 in 4, Grade 2 in 3, and Grade 3 in 4), diffuse large B-cell in 14, peripheral T-cell lymphoma in 2, Burkitt-like in 1, mantle cell in 2, natural killer cell in 2, plasmacytoma/lymphoma in 1, and T-cell lymphoblastic in 1. The initial treatment was chemotherapy in 32 patients (94%); 71% were refractory to initial chemotherapy and 29% developed a relapse after an initial response. The RT response was complete in 24% (n = 8), complete, unconfirmed in 26% (n = 9), partial in 47% (n = 16), and none in 3% (n = 1). The local control rate was 73% at 1, 2, and 3 years. Grade 1 dermatitis was the most common side effect. Hyperfractionated RT provided good local control and was well tolerated. This encouraging result requires additional study with comparison to conventional fractionation regimens.

French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1-->D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1-->D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3. A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an "aggressive" dose-intensity radiotherapy schedule.

Organ Preservation and Treatment Toxicity With Induction Chemotherapy Followed by Radiation Therapy or Chemoradiation for Advanced Laryngeal Cancer

The authors reviewed records of patients with advanced laryngeal cancer treated with induction chemotherapy (IC) and hyperfractionated radiation therapy (RT) or chemoradiation (CRT) to determine the rates of organ preservation and function. A total of 29 patients with stage III (45%) and stage IV (55%) squamous cell carcinoma of the larynx (SCCL), were treated with IC and RT or CRT in 1 of 7 consecutive trials. Fifty-five percent had clinically node-positive disease. Fifty-five percent and 45% had T3 or T4 tumors, respectively. All received 3 cycles of platinum-based IC. Daily RT was given to 48%, twice-daily RT to 45%, and concomitant boost RT to 7%. CRT was carboplatin (28%) or docetaxel (28%). Those treated with twice-daily RT did not receive CRT. The median follow-up is 52 months. Overall survival is 66%. Relapse occurred in 12 patients (41%), and 6 underwent salvage laryngectomy (5 stage III, 1 stage IV). Fifty-nine percent of patients (17 of 29) are alive at last follow-up with an anatomically intact larynx, and 48% (14 of 29) are alive with a functional larynx. Of the 23 patients for whom detailed information on gastrostomy tube (g-tube) placement/removal was available, median time with g-tube was 12 months, and 15 of 23 patients (65%) had a g-tube for 6 months or more. Twenty-three of all 29 patients (79%) retained an anatomically intact larynx, but 7 of 23 (30%) never resumed their pretreatment organ function. The overall rate of functional organ preservation, regardless of survival, was 55% (16/29). The 7 of 29 patients (26%) who retained a nonfunctional larynx required permanent g-tube or were unable to return to pretreatment oral intake capability. Nine of 13 with T4 SCCL (69%) compared with 7 of 16 (44%) T3 SCCL retained a functional larynx. The rate of larynx preservation is high, but toxicity remains significant with IC followed by hyperfractionated RT or CRT in advanced laryngeal cancer. Half of all patients were alive, able to retain their larynx, and return to pretreatment function. Advanced stage was not an indicator of poor outcome.

P-797 Combination chemotherapy including topotecan concurrentlywith twice-daily radiotherapy in limited SCLC. A phase II trial of the Danish Oncological Lung Cancer Group (DOLG)

P-797 Combination chemotherapy including topotecan concurrentlywith twice-daily radiotherapy in limited SCLC. A phase II trial of the Danish Oncological Lung Cancer Group (DOLG)

Creeping Phase II-ism and the Medical Pharmaceutical Complex: Weapons of Mass Distraction in the War Against Lung Cancer

This issue reports the long-awaited Radiation Therapy Oncology Group (RTOG) phase II study that incorporated paclitaxel, the new drug of the 1990s, with standard twice-daily radiotherapy and cisplatin plus etoposide, which was presented initially at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO) in 2000. In that abstract, the authors addressed the following questions. Can the addition of paclitaxel to etoposide and cisplatin result in improved survival for patients with limited small-cell lung cancer (SCLC)? Can the addition of paclitaxel improve on the results (1-year survival of 70% and median survival of 23 months) of the best arm of the Intergroup study? They reported that the 1-year survival rate on their study was 83%, inferring an advantage at this unorthodox benchmark, but the median survival had not yet been reached. Ettinger et al have more carefully modified their prose in preparing this final report for the trial and parsed every phrase to diligently inform all and offend no one. At the end of the day, the addition of paclitaxel to etoposide plus cisplatin provides no advantage to standard treatment without paclitaxel, which is similar to the conclusion of the results of the extensive disease trial that incorporated these three drugs. Moreover, as in most lung cancer trials, the third drug adds toxicity without survival benefit. Unlike this sober and direct final report and the abstract on the phase III study in extensive-disease SCLC, the original abstract and preliminary presentation of these data perhaps over-optimistically forecast the survival benefit for this threedrug combination administered with concurrent twice-daily radiotherapy. We are all enthusiastic about our work and interested that the world should know about its promise. But, is it really useful news that the abstract proffered information that was ultimately misleading about the final outcome and importance of the study? This was a phase II cooperative group trial initially reported as a preliminary result. Although it may not be news, there are unintended consequences of the practice of magnifying the importance of such preliminary results at the Annual Meetings of ASCO and creating too much enthusiasm for phase II study results. A San Francisco newspaper expressed concern to ASCO that the data presented at these meetings and in the abstract book might “move the market” and represent “insider trading” (perhaps a concern for an entirely different editorial in the future). I am more concerned that such reports move the hearts and minds of the clinical practice community, perhaps too soon for these preliminary results. At the same time, such preliminary reports also throw clinical research into a state of uncertainty. Determining what is truly promising from what is hyperbole can be quite difficult with too early results. Sometimes, we as authors stretch to find a measure that makes results seem better or more important than they are. We have to be particularly cautious about phase II results, preliminary or otherwise, and downright dubious about fanciful claims and novel end points, such as 1-year survival, in lung cancer or any other disease. Paclitaxel promised great hope in lung cancer, but now that results of mature trials are available, it has produced some frankly disappointing results compared with our initial expectations. It is clearly not as good as the lung cancer pundits forecasted or preached at advisory boards. Obviously, paclitaxel has some activity, but despite a different mechanism of action and toxicity profile from cisplatin and etoposide, it does not seem to add significant benefit to those drugs in SCLC. Similarly, there is a real issue as to whether it is better, the same, or not as good in locally advanced or metastatic non–smallcell lung cancer (NSCLC). A final report at the ASCO Annual Meeting in 1998 of a randomized phase III study of paclitaxel has not, as yet, seen publication in a peer-reviewed journal. Are paclitaxel combinations really better than cisplatin plus etoposide for SCLC or NSCLC? I can ask this about paclitaxel JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 22 AUGUST 1 2005