Continuous Infusion Of Cisplatin Research Articles

Therapeutic Strategy of Advanced Hepatocellular Carcinoma by Using Combined Intra-Arterial Chemotherapy

The majority of primary liver cancer is hepatocellular carcinoma (HCC). HCC has increased in many countries, particularly where hepatitis C virus infection is more common than hepatitis B virus infection. Several non-surgical treatment options, including transcatheter arterial embolization, percutaneous ethanol injection, microwave coagulation, and radiofrequency ablation have been developed and are widely used for unresectable HCC. However, these modalities are not indicated for patients with multifocal disease, invasion or thrombosis of major blood vessels, and poor liver function. The majority of patients with advanced hepatocellular carcinoma (aHCC) do not survive for longer than 6 months from the time of diagnosis. Combined intra-arterial chemotherapy is one of the few remaining options for patients with aHCC. Continuous local arterial infusion of 5-fluorouracil (5-FU) and cisplatin (CDDP) via an infuser pump and implanted reservoir has been shown to prolong the survival of patients with aHCC. When LC patients with aHCC undergo chemotherapy, we should consider the influence of both tumor factors and host immunity. This review focuses on therapeutic strategy of patients with aHCC by using combined intra-arterial chemotherapy and the influence of host immunity on the response to such chemotherapy based on our results. The present article shows some recent patents related to the field.

Treatment of Hepatocellular Carcinoma Using Arterial Chemoembolization with Degradable Starch Microspheres and Continuous Arterial Infusion of 5-Fluorouracil

Transcatheter arterial embolization (TAE) with gelatin sponge particles and iodized oil often yields poor results when used to treat unresectable multifocal hepatocellular carcinoma (HCC). The present study retrospectively investigated the utility of a novel combination chemotherapy regimen for treating multifocal HCC resistant to TAE. Thirteen consecutive patients with unresectable multifocal HCC and resistance to TAE were treated with combination chemotherapy consisting of arterial chemoembolization with degradable starch microspheres (DSM) (150-4500 mg on Day 1), mitomycin-C (4-8 mg on Day 1), continuous arterial infusion of 5-fluorouracil (1250 mg/120 h), cisplatin (25-50 mg/120 h) and l-leucovorin (125 mg/120 h) for 10-19 weeks. The response rate was 84.6%, with complete response in one patient and partial response (PR) in 10 patients. In four of 10 patients with PR, the tumor was not observable, although the tumor marker did not completely decline to the normal range. The 1-, 2- and 3-year survival rates were 100, 28.9 and 9.6% in all, and 100, 33.3 and 0% in six patients with portal vein tumor thrombosis (PVTT). The median survival was 22.1 months in all and 17.1 months in six patients with PVTT. Thrombocytopenia of Grade III or higher was observed in eight patients. Laparoscopic splenectomy was performed before therapy in four patients with platelet counts of <70,000/mm(3), and during therapy in five patients with severe thrombocytopenia. This novel chemotherapy regimen achieved favorable results and may be useful in treating patients with unresectable multifocal HCC resistant to TAE.

Concurrent chemoradiotherapy with cisplatin and fluorouracil for locally advanced hypopharyngeal carcinoma

Conclusions. The concurrent administration of cisplatin and fluorouracil (CCRT) during radiotherapy after induction chemotherapy had better results than induction chemotherapy followed by radiotherapy alone (CT+RT) for overall survival, laryngeal preservation, and locoregional control in patients with locally advanced hyopharyngeal cancer. Objectives. To report treatment results comparing CCRT with CT+RT in locally advanced hypopharyngeal cancer. Patients and methods. Sixty-six consecutive patients treated with curative intent were analyzed retrospectively. Thirty-eight patients were treated with induction chemotherapy followed by definitive RT, and 28 patients with induction chemotherapy followed by concurrent chemoradiotherapy. All patients had more than three cycles of continuous infusion of cisplatin and 5-fluorouracil every 3 weeks. The median dose of irradiation was 70 Gy in the CT+RT group and 68.4 Gy in the CCRT group, respectively. Results. The overall 5-year survival rates were 24% for the CT+RT group and 42% for the CCRT group (p=0.031). The 3-year pharyngolaryngectomy-free survival rates were 32% for the CT+RT group and 63% for the CCRT group (p=0.032). The 3-year locoregional control rate for CCRT was significantly better than that for the CT+RT (52% vs 23%, p=0.004). Acute hematologic toxicity appeared in 39% of the CT+RT patients and 75% of the CCRT patients.

Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3

Total therapy 3 incorporated bortezomib into a melphalan-based tandem transplant regimen for 303 newly diagnosed patients with myeloma. Induction chemotherapy prior to and consolidation chemotherapy after transplants each consisted of two cycles of VTD-PACE (bortezomib, thalidomide, dexamethasone and 4-d continuous infusions of cis-platin, doxorubicin, cyclophosphamide, etoposide); 3-year maintenance comprised monthly cycles of VTD in the first and TD in the remaining years. The median age was 59 years (age >64 years, 28%). A minimum of 20 x 10(6) CD34 cells/kg was collected in 87% of patients; 83% completed both transplants, and only 5% suffered a treatment-related death. At 24 months, 83% had achieved near-complete remission, which was sustained in 88% at 2 years from its onset. With a median follow-up of 20 months, 2-year estimates of event-free and overall survival were 84% and 86% respectively. The 44 patients who experienced an event more often had a high-risk gene array profile, cytogenetic abnormalities and indicators of high lactate dehydrogenase, beta-2-microglobulin, creatinine and International Staging System stage. Toxicities of grade > 2 included thrombo-embolic events in 27% and peripheral neuropathy in 12%. Results of this phase-2 study demonstrated that bortezomib could be safely combined with multi-agent chemotherapy, effecting near-complete remission status and 2-year survival rates in more than 80% of patients.

A Phase II Trial of Accelerated Multimodality Therapy for Locoregionally Advanced Cancer of the Esophagus and Gastroesophageal Junction

This is a report of mature results from a phase II trial of an accelerated multimodality treatment program for locoregionally advanced cancer of the esophagus and gastroesophageal junction with a focus on the impact of clinical heterogeneity on outcomes. A split course of pre- and postoperative hyperfractionated radiation therapy and concurrent chemotherapy was used in an effort to limit perioperative mortality. Eligibility required a diagnosis of esophageal or gastroesophageal junction cancer and an esophageal ultrasound stage of at least T3, N1, or M1A. Patients received a 12-day induction course of radiation (1.5 Gy twice a dose to a dose of 30 Gy) concurrent with 4-day continuous intravenous infusions of cisplatin (20 mg/m2 per day) and 5-fluorouracil (1000 mg/m2 per day) beginning on day 1. Surgery followed in 4 to 6 weeks followed 6 to 10 weeks later by a second, identical course of chemoradiotherapy. From October 1999 through March 2003, 93 patients were enrolled; 96% were white, 86% male, and 83% had adenocarcinoma. Resection was possible in 83 patients (89%) with 4 (5%) perioperative deaths. With a median follow up of 50 months (range, 34-72 months), the 3-year projected overall survival rate is 27.9%, freedom from recurrence 30.5%, and distant metastatic control 32.4%. Locoregional control in resected patients is 86%. Freedom from recurrence and distant control were significantly better in patients with 1) earlier pretreatment clinical stage, 2) earlier postinduction pathologic stage, 3) squamous cell cancer, and 4) a pathologic response. This accelerated multimodality treatment program is feasible and perioperative mortality proved acceptable. Despite excellent locoregional control, freedom from recurrence, and overall survival proved disappointing reflecting the frequency of distant metastases. Heterogeneity in patient populations makes comparisons with similar nonrandomized experiences problematic.

Treatment of Metastatic or Recurrent Gastric Cancer with Weekly 24-hour Infusion of Cisplatin and High-Dose 5-Fluorouracil/Leucovorin in an Outpatient Setting

Objective: There is no general agreement over a standard chemotherapy regimen for metastatic or recurrent gastric cancer. We evaluated, retrospectively, the activity and toxicity of weekly 24-hour infusion of cisplatin with high-dose 5-fluorouracil/leucovorin (P-HDFL) in an outpatient setting. Materials and Methods: Patients with metastatic or recurrent gastric cancer, treated in an outpatient setting from May 2001 to July 2005, were analyzed retrospectively. The regimen consisted of continuous infusion cisplatin 25mg/m^2, 5-fluorouracil 2000 mg/m^2 and leucovorin 200mg/m^2 on day 1, 8 and 15 every 4 weeks. The treatment was continued for a maximum of six cycles unless the disease progressed or intolerable toxicities occurred. Results: Twenty-one patients received this regimen: 16 men and 5 women, median age 56 years (range 27-71). A median of 4.3 cycles was administered. Seven of 21 patients (33.3%) achieved an objective partial response. Stable disease was observed in 6 patients (28.6%) and progressive disease in 8 patients (38.1%). The median survival was 7.7 months (95% confidence interval, 6.2-12.8 months). Digestive and hematological toxicities were low and no severe renal insufficiency was observed. The most common toxicity was elevated liver enzymes (11 patients, 52%), of whom three had≥grade 3 toxicity: 1 of them died of hepatic failure. Conclusion: Our results show that outpatient P-HDFL therapy leads to a fairly comparable outcome with various regimens of 5-fluorouracil/cisplatin. This outpatient regimen could be a reasonable alternative that combines advantages in respect of patient activity, mild to moderate toxicity, convenience of dosing and minor expenditure.

Retrospective analysis: concurrent chemoradiotherapy using protracted continuous infusion of low-dose cisplatin and 5-fluorouracil for T2N0 glottic cancer

Treatment with conventional radiotherapy alone for local control of T2 glottic cancer (T2GC) is insufficient. To improve local control of T2GC, we have simultaneously administered continuous intravenous infusions of low-dose cisplatin and 5-fluorouracil (5-FU) in combination with irradiation. We performed this combination therapy in a total of 11 consecutive patients with previously untreated invasive squamous cell carcinoma (T2GC). Cisplatin was administered at 4 mg/m2/day and 5-FU at 200 mg/m2/day for 120 h, except during weekends, beginning on the day irradiation with a once-daily fraction at 2 Gy was started. An initial local control rate of the primary tumor was achieved in 10 of the 11 patients (91%), and ultimate laryngeal preservation by cordectomy was achieved in all cases. Regarding adverse reactions, grade 3 or 4 hemotoxicity did not develop in any of the patients. Grade 3 laryngitis was observed in four patients (36%), but none of these patients required interruption of treatment owing to acute laryngeal reactions. Instead of radiotherapy alone, this combination chemoradiotherapy is suggested with the possibility of improving local control of T2GCs.

Multiagent Concurrent Chemoradiotherapy for Locoregionally Advanced Squamous Cell Head and Neck Cancer: Mature Results From a Single Institution

A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer. Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease. With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors. Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.

Low Incidence of Ototoxicity With Continuous Infusion of Cisplatin in the Treatment of Pediatric Germ Cell Tumors

Cisplatin is an important chemotherapeutic agent in the treatment of many pediatric malignancies, but its use is limited in part by ototoxicity. The authors' institution has been administering standard-dose cisplatin by continuous infusion rather than bolus administration in germ cell tumors. The authors retrospectively reviewed 39 patients with germ cell tumors requiring chemotherapy over the past 20 years and recorded data including demographics, cumulative cisplatin dose, degree of ototoxicity (by the Brock grading system), and disease outcome. The median age was 9.4 years and the majority of children (48.7%) had endodermal sinus tumor. Twenty-one children received 400 mg/m of cisplatin or more. One child had evidence of significant ototoxicity at last follow-up (6.64 years after diagnosis). This patient received a total cumulative dose of 500 mg/m of cisplatin. Eighty-two percent of children achieved clinical remission of their disease. The authors conclude that continuous administration of cisplatin is associated with minimal ototoxicity while maintaining good tumoricidal efficacy, and further studies using this regimen are warranted.

Efficacy of continuous venous infusion of fluorouracil and consecutive low-dose cisplatin as adjuvant treatment in resectable colorectal cancer: a prospectively randomized trial

3696 Background: Low-dose cisplatin (CDDP) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin. On the other hand, in Japan, adjuvant therapy using oral fluoropyrimidines after curative resection of a colorectal tumor has been achieved since the 1980s. For many years, oral fluoropyrimidines have been frequently used in the adjuvant setting for curatively resected colorectal cancer. We performed a randomized trial to compare the efficacy and toxicity of a continuous venous infusion of 5-FU plus low-dose CDDP (low-dose FP) treatment followed by oral 5-FU with those of oral 5-FU alone in Dukes’ B and C colorectal cancer in the adjuvant setting. Methods: One hundred and eighty-two patients were enrolled. Patients were randomly assigned to receive a treatment of low-dose FP (5-FU; 320 mg/m2, days 1–21, CDDP; 3.5 mg/m2 daily for 21 days) followed by oral 5-FU (200 mg/day daily for 2 years) or an oral 5-FU treatment (200 mg/day daily for 2 years) exclusively. Results: The 5-year disease-free survival (DFS) and the 5-year overall survival (OS) indicated no significant difference between the two groups. By stratified analysis, in the colon cancer patients, the DFS in patients receiving low-dose FP treatment was significantly increased: 93.5% in the FP treatment group as compared with 76.9% in the oral 5-FU group (p=0.024). However, in the rectal cancer patients, there was no difference between the oral 5-FU group and the low-dose FP treatment group (5-year DFS; 60.0% vs. 59.4%, p=0.887). After covariate adjustment, the low-dose FP treatment improved the hazard risk of relapse in the colon cancer patients (HR=0.301, 95%CI. 0.081–1.115, p=0.072). Grade 3–4 toxicities were low in the two groups. Conclusions: In the overall analysis, this study failed to show improvement in DFS or in OS. However, the subgroup with colon tumors treated with low-dose FP followed by oral 5-FU seemed to have a DFS advantage in comparison with the oral 5-FU treatment. Low-dose FP has mild toxicities and is a tolerable regimen. These data suggest that low-dose FP followed by oral 5-FU is a feasible regimen for cancer patients with a resected colon cancer patients. No significant financial relationships to disclose.

A Phase II Study of Docetaxel and Infusional Cisplatin in Advanced Non-Small-Cell Lung Cancer

Background: To evaluate the efficacy and safety of combination chemotherapy of cisplatin (5-day continuous infusion) and docetaxel for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC). Materials and Methods: Eligible patients had an ECOG performance status of 0–2 with measurable NSCLC. Patients received continuous infusion cisplatin 20 mg/m²/day on 5 days and bolus docetaxel 60 mg/m²/day (day 1; PiD therapy) at a 4-week interval. Results: Forty-three patients were enrolled. The mean number of cycles administered per patient was 2, and ranged from 1 to 4. The response rate was 49% (95% confidence interval, 33.9–63.8%). The median survival time was 47 weeks and the 1-year survival rate was 47%. The major toxic effects were grade 3 or 4, neutropenia (88%), leukopenia (81%), thrombocytopenia (14%) and anemia (42%). There were no treatment-related deaths. Conclusion: PiD therapy was a well-tolerated and active regimen for patients with advanced NSCLC. The major toxicity was neutropenia.

A phase II trial of continuous infusion of 5‐fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma

The aim of the current study was to evaluate the antitumor activity and toxicity of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin (FMP therapy) in chemotherapy-naive patients with metastatic hepatocellular carcinoma (HCC). Fifty-one patients with metastatic HCC who had not undergone previous systemic chemotherapy were enrolled. The therapy consisted of intravenous administration of 80 mg/m2 cisplatin and 6 mg/m2 mitoxantrone on Day 1 and continuous intravenous infusion of 450 mg/m2 5-fluorouracil per day on Days 1-5. The treatment was repeated every 4 weeks for a maximum of 6 courses with dose adjustments based on the observed toxic effects if there was no evidence of tumor progression or unacceptable toxicity. Of the 51 enrolled patients, 14 (27%) achieved a partial response (95% confidence interval, 16-42%) with a median duration of 7.6 months (range, 2.3-18.4 months). Twenty-seven patients (53%) showed no change and 9 (18%) had progressive disease. The median survival time, 1-year survival rate, and median progression-free survival time for all patients were 11.6 months, 44.3%, and 4.0 months, respectively. The main Grade 3 and 4 toxicities were leukocytopenia (67%), neutropenia (71%), thrombocytopenia (27%), and elevated levels of aspartate aminotransferase (37%) and alanine aminotransferase (41%). These symptoms were generally brief and reversible, with the exception of one treatment-related death due to acute hepatic failure. FMP therapy had significant antitumor activity with acceptable toxicity in patients with metastatic HCC.

Hematopoietic Progenitor Cell (HPC) Mobilization after Initial Therapy of Multiple Myeloma Including Velcade: Ability to Collect HPC as a Function of Velcade Dosing.

Bortezomib (Velcade) was recently approved by the US FDA for use as salvage therapy for patients with relapsed multiple myeloma (MM). We are conducting a clinical trial (Total Therapy 3) using VDT-PACE (velcade 1.0 mg/m2, dexamethasone 40 mg po QD day4–7, thalidomide 200 mg po QHS day 4–7, and continuous infusion of cisplatin 10 mg/m2, doxorubicin 10 mg/m2, and etoposide 40 mg/m2 day 4–7) and G-CSF at 5-8 mcg/Kg sc BID for initial therapy of MM as well as for mobilization of HPC for collection and use in autologous stem cell transplant. Initially, 20 patients (pts) were enrolled in 6 cohorts involving an escalating number of bortezomib doses: cohort 1 (5 pts) had 2 doses with cycle 1 and then underwent HPC collection; cohort 2 (3pts) had 3 doses with cycle 1 and then collection; cohort 3 (3 pts) had 4 doses with cycle 1 and then collection; cohort 4 (3 pts) had 4 doses with cycle 1, 2 doses with cycle 2 and then underwent HPC collection; cohort 5 (3 pts) had 4 doses with cycle 1 and 3 doses with cycle 2 and then collection; cohort 6 (3pts) had 4 doses with cycle 1 and 4 doses with cycle 2 and then collection. Further pts (cohort 7) were then treated and underwent HPC collection as for cohort 6. The protocol required a minimum of 2 HPC collections, and all patients underwent large volume leukapheresis using a Cobe Spectra when the peripheral blood CD34 measured by ProCount™ predicted a collection of ≥ 1 x 106/kg (Hematology (ASH Educat Progr) 2003; 419–37). HPC product contamination with malignant plasma cells was done using flow cytometry for cytoplasmic immunoglobulins (cIg). Patients who failed to mobilize adequately to support a tandem transplant were enrolled on a study utilizing G-CSF+AMD3100 for mobilization.HPC Collections by Cohort# Ptsmedian # Collections (range)mean CD34x106/Kg (range)Cohort 15231.2 (19.8–47.8)Cohort 23*252.4 (45.1–59.6)Cohort 33245.3 (31.9–80.5)Cohort 432 (2–3)#22.9 (5.9–40.9)Cohort 532 (2–4)44.8 (18.2–85.5)Cohort 632 (2–3)36.1 (22.6–47.1)Cohort 7243 (0–9)+17.5 (0–30.8)*1pt died before collection #1 pt switched to AMD3100 +6 pts switched to AMD3100The median number of HPC collections for the first 6 cohorts overall was 2, and contamination as judged by cIg was very rare (2 of 19 who underwent collection). However, while 1 pt in cohort 4 failed to mobilize adequately with the planned regimen and required transfer to the secondary mobilization study, 6 of the first 24 pts in cohort 7 failed to mobilize and also required transfer to the secondary mobilization study. Of the first 27 patients evaluable after first transplant, both granulocyte and platelet recovery proceeded promptly. Because of the apparent dampening of cycle 2 PBSC mobilization, future patients are mobilized during cycle 1. Incorporation of Velcade into PBSC mobilization regimens should therefore proceed with caution.

Total Therapy 3 (TT 3) for Newly Diagnosed Myeloma, Incorporating Velcade into Remission Induction with DT PACE: Early Results Regarding Efficacy, PBSC Mobilization and Toxicities.

TT 3 represents a further development of the Total Therapy concept after completion of accrual to TT 2 with 668 patients. Based on the high salvage potential of the Velcade + Thal + Dex (VTD) regimen for endstage MM, VTD had been added to PACE (4 day continuous infusions of cisplatin 10 mg/m2, adriamycin 10 mg/m2, cyclophosphamide 400 mg/m2 and etoposide 40 mg/m2) x 2 cycles for induction with PBSC collection with first or second cycle; followed by MEL 200 mg/m2-based autotransplant 2–3 months apart and subsequent consolidation therapy with further VTD PACE and VTD maintenance. As of July 1, 2004, allowing for a 1-month time to evaluate initial response and toxicity, 57 patients have been accrued to TT 3. M protein responses by level demonstrated ≥ near-CR in 16% prior to cycle 2; 26% after cycle 2 prior to first transplant and nearly 40% after first transplant (patients not yet evaluable for response for a particular step were considered non-responders; intent-to-treat analysis). The PBSC collection target of 20 million CD 34 cells/kg was accomplished within 2 days of collection in all 10 patients mobilized on the first cycle; among 29 patients collected on the second cycle, 17 collected at least 20 million CD 34 cells/kg during 2–3 days, especially when only 2 or 3 doses of Vel 1.0 mg/m2 were applied, whereas in case of 4 doses (day −2, +1, +5, +8) 5 of 23 patients failed to collect on this cycle and 13 reached ≥ 20 x 106/kg procurement goal. There was only 1 treatment-related death in a setting of renal failure at diagnosis. Other toxicities were mainly myelosuppression whereas non-hematologic toxicities appeared to be similar to those seen with DT PACE previously. Laboratory correlates such as gene expression profiling, after a test dose of Velcade and after VTD PACE along with early suppression of FDG uptake on PET will also be presented. These preliminary data indicate remarkable activity and safety of a regimen that incorporates all available drugs with single agent activity in a multi-combination strategy, aimed at maximizing and accelerating tumor mass reduction in an effort to overcome the negative consequences especially of metaphase cytogenetic abnormalities.

Combination chemotherapy (cyclophosphamide, doxorubicin, and vincristine with continuous-infusion cisplatin and etoposide) and radiotherapy with stem cell support can be beneficial for adolescents and adults with estheisoneuroblastoma.

Adolescent-onset and adult-onset esthesioneuroblastoma is a rare disease and is considered incurable. In many patients, local resection and radiation are chosen as clinical therapy with or without chemotherapy. It was reported previously that local resection and radiotherapy led to temporary remission and, in many patients, recurrent disease. Although combination with chemotherapy has been regarded as promising, an effective regimen has not been established. In the current study, the authors investigated the effect and tolerability of the combination of chemotherapy, radiotherapy, and peripheral blood stem cell transplantation (PBSCT). The study population included 12 patients with adolescent-onset and adult-onset esthesioneuroblastoma classified as Kadish Stage A-D. The patients received two cycles of combination chemotherapy, which consisted of cyclophosphamide, doxorubicin, and vincristine (CAD) with continuous-infusion cisplatin and etoposide (CVP). This was combined with radiotherapy with or without PBSCT. Nine of 12 patients (75%) obtained more than a partial response after only 2 cycles of chemotherapy. After radiation with or without PBSCT, six patients obtained a complete remission (CR). The longest survival was > 3 years. All patients who underwent PBSCT obtained a CR. The most severe side effects were loss of sodium and potassium induced by cisplatin-related renal tubular distress. Those abnormalities were temporary, and all patients recovered. The chemotherapy regimen with CADO and CVP does not require continuation for a long time and is very effective and tolerable for patients with adolescent-onset and adult-onset esthesioneuroblastoma. The combination with radiotherapy and PBSCT may lead to a CR without facial disfigurement. In this report, the authors discuss the feasibility and efficacy of this multidisciplinary approach.

Concomitant chemo-radiotherapy with continuous infusion cisplatin and 5-fluoruracil in locally advanced cervical carcinoma (LACC): A single institution experience

5073 Background: The primary aim of this analysis was to evaluate the resecability of LACC (stage IIA-IIIB) and the relationship between downstaging, progression-free-survival (PFS) and overall survival (OS) after neoadjuvant concomitant chemo-radiotherapy (CT-RT). Secondary aim was the assessment of activity and tolerability of such approach. Methods: Pts affected by LACC were planned to receive 50.4 Gy external beam RT (EBRT, boost included) plus concomitant CT with cisplatin (DDP) 5 mg/m2/day i.v. and 5-fluorouracil (5FU) 200 mg/m2/day i.v., day 1–5, for scheduled 5 weeks. After restaging, patients not suitable for curative resection were treated with additional 25 Gy EBRT. Scheduled surgical procedures were radical hysterectomy plus pelvic lymphadenectomy (PIVER II/III), according to clinical response. Results: Forty-nine pts with LACC referred to our Institution; pts characteristics: median age 55 (range 32–78); stage IIA/IIB/IIIA/IIIB 3pts/34pts/2pts/9pts; squamous cell LACC/adenocarcinoma 45/4. Thirty-two pts (65.3%) received 4–5 weeks of concurrent CT-RT (median RT dose 50.4 Gy, range 46–57.6) and underwent surgical resection. Twelve pts obtained CR (37.4%, 95% CI 20.7–54.3), 14 pts PR (43.8%, 95% CI 26.6–60.9), and 6 pts NC (18.8%, 95% CI 5.2–32.3). Seventeen pts (34.7%) received additional 2–3 weeks of concurrent CT-RT (median RT dose 25 Gy) without surgery. Of these, 3 pts had RC (17.6%, 95% CI 0–35.8), 6 pts PR (35.3%, 95% CI 12.6–58), 4 pts NC (23.5%, 95% CI 3.4–43.7), 3 pts PD (17.6%, 95% CI 0–35.7), and 1 pts NV. No CTC Grade 4 toxicity was observed; only 3 pts had G3 diarrhea. At a median follow-up of 18 months (range 3–84), 5-yrs-PFS in all pts was 60.5%, and 5 yrs-OS 56.9%. Five-yrs PFS and survival rate were significantly greater in pts undergone surgery (respectively p=0.03 and p=0.0001). Conclusions: Neoadjuvant concurrent CT-RT is tolerable, active and affect resecability owing to tumor shrinking. Moreover, the data seems to indicate that curative surgery improves 5-yrs OS. No significant financial relationships to disclose.

Concomitant chemo-radiotherapy with continuous infusion cisplatin and 5-fluoruracil in locally advanced cervical carcinoma (LACC): A single institution experience

Concomitant chemo-radiotherapy with continuous infusion cisplatin and 5-fluoruracil in locally advanced cervical carcinoma (LACC): A single institution experience

Long-term follow-up after chemoradiotherapy (CRT) and surgery in patients (pts) with stage III non-small cell lung cancer (NSCLC): Is bulky mediastinal nodal disease of prognostic importance

7168 Background: Bulky mediastinal nodal involvement at presentation has been considered a poor prognostic factor in pts with stage III NSCLC. We present long-term follow-up from a phase II trial of accelerated fractionation radiation (AFR), concurrent chemotherapy and surgery, to address this issue. Methods: Between 10/94 and 9/00, 105 pts with surgically proven stage IIIA (N=78) or IIIB (N=27) NSCLC underwent induction treatment consisting of a 96-hour continuous cisplatin infusion (20 mg/m2/day) and a 24-hour infusion of paclitaxel (175 mg/m2) concurrent with AFR (1.5 Gy bid) to a dose of 30 Gy. Surgery was scheduled 4 weeks later, with a second identical course of CRT given 4–6 weeks post-operatively to a total dose of 60–63 Gy. Results: With a median follow-up of 59 (range 35–102) months, the projected Kaplan-Meier (KM) 5-year overall survival is 29%. KM 5-year locoregional and distant control are 85% and 39% respectively. KM 5-year survival was better in clinical stage IIIA vs. IIIB pts (33% vs. 19%, P=0.03); clinical responders to induction vs. non responders (36% vs. 17%, P=0.004); and pathologic responders vs. non-responders (45% vs. 11%, P < 0.001). Pathologic stage after surgery also predicted 5-year survival (stage 0-II: 55%; IIIA: 23%; IIIB - IV: 4%; P < 0.001). Pre-treatment mediastinoscopy identified 20 pts with only microscopic intra-nodal involvement in one or more ipsilateral nodes, and 61 pts with gross macroscopic, but ipsilateral, nodal disease. These two groups did not differ in median or 5-year KM survival (27 vs. 29 months, 45% vs. 27%, P= 0.45). The extent of ipsilateral nodal involvement contributed no prognostic information about survival in a Cox multivariable analysis. Conclusions: Clinical stage IIIA disease, clinical and pathologic response to induction, and a lower pathologic stage are important predictors for survival after this CRT protocol for pts with stage III NSCLC. Bulky ipsilateral mediastinal nodal involvement at diagnosis is of no prognostic importance for survival in these pts and should not be a consideration in treatment planning. No significant financial relationships to disclose.

Long-term follow-up after chemoradiotherapy (CRT) and surgery in patients (pts) with stage III non-small cell lung cancer (NSCLC): Is bulky mediastinal nodal disease of prognostic importance

7168 Background: Bulky mediastinal nodal involvement at presentation has been considered a poor prognostic factor in pts with stage III NSCLC. We present long-term follow-up from a phase II trial of accelerated fractionation radiation (AFR), concurrent chemotherapy and surgery, to address this issue. Methods: Between 10/94 and 9/00, 105 pts with surgically proven stage IIIA (N=78) or IIIB (N=27) NSCLC underwent induction treatment consisting of a 96-hour continuous cisplatin infusion (20 mg/m2/day) and a 24-hour infusion of paclitaxel (175 mg/m2) concurrent with AFR (1.5 Gy bid) to a dose of 30 Gy. Surgery was scheduled 4 weeks later, with a second identical course of CRT given 4–6 weeks post-operatively to a total dose of 60–63 Gy. Results: With a median follow-up of 59 (range 35–102) months, the projected Kaplan-Meier (KM) 5-year overall survival is 29%. KM 5-year locoregional and distant control are 85% and 39% respectively. KM 5-year survival was better in clinical stage IIIA vs. IIIB pts (33% vs. 19%, P=0.03); clinical responders to induction vs. non responders (36% vs. 17%, P=0.004); and pathologic responders vs. non-responders (45% vs. 11%, P < 0.001). Pathologic stage after surgery also predicted 5-year survival (stage 0-II: 55%; IIIA: 23%; IIIB - IV: 4%; P < 0.001). Pre-treatment mediastinoscopy identified 20 pts with only microscopic intra-nodal involvement in one or more ipsilateral nodes, and 61 pts with gross macroscopic, but ipsilateral, nodal disease. These two groups did not differ in median or 5-year KM survival (27 vs. 29 months, 45% vs. 27%, P= 0.45). The extent of ipsilateral nodal involvement contributed no prognostic information about survival in a Cox multivariable analysis. Conclusions: Clinical stage IIIA disease, clinical and pathologic response to induction, and a lower pathologic stage are important predictors for survival after this CRT protocol for pts with stage III NSCLC. Bulky ipsilateral mediastinal nodal involvement at diagnosis is of no prognostic importance for survival in these pts and should not be a consideration in treatment planning. No significant financial relationships to disclose.

Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer?

The role of neck dissection (ND) after definitive chemoradiotherapy for squamous cell head and neck cancer is incompletely defined. We retrospectively reviewed 109 patients with N2-N3 disease treated with chemoradiotherapy to identify predictors of a clinical complete response in the neck (CCR-neck), pathologic complete response after ND (PCR-neck), and regional failure. All patients were given 4-day continuous infusions of 5-fluorouracil (1000 mg/m2/d) and cisplatin (20 mg/m2/d) during the first and fourth weeks of either once daily (n = 68) or twice daily (n = 41) radiation therapy. ND was considered for all patients after completion of chemoradiotherapy and was performed in 32 of the 65 patients achieving a CCR-neck after chemoradiotherapy and in all 44 patients with residual clinical evidence of neck disease. CCR-neck, PCR-neck, and regional failure were then correlated with potential predictors, including T, N, largest lymph node size (<3 cm, > or =3 cm), primary tumor site, and radiation fractionation schedule. Achievement of a CCR-neck was predicted by N, N2 vs N3 (53 of 80 vs 12 of 29, p =.019) and by largest lymph node size, <3 cm vs > or =3 cm (19 of 25 vs 46 of 84, p =.06). Achievement of a PCR-neck could not be predicted by any clinical parameter. Regional failure occurred both in patients undergoing ND and those not dissected (5 of 76 vs 4 of 33, p =.33) and proved more likely only in the ND patients with residual positive pathology compared with those achieving a PCR-neck (5 of 25 vs 0 of 51, p <.001). Primary site was not a useful predictor of CCR-neck, PCR-neck, or regional failure. Most importantly, CCR-neck (vs <CCR-neck) did not predict either a PCR-neck (24 of 32 vs 27 of 44, p =.21) or regional failure (5 of 65 vs 4 of 44, p =.80). After chemoradiotherapy, clinical parameters do not identify those patients with residual neck node disease or those at risk for regional failure, suggesting that ND be considered for all N2-N3 patients.