Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy.

1992 ◽  
Vol 10 (1) ◽  
pp. 79-84 ◽  
Author(s):  
B D Minsky ◽  
A M Cohen ◽  
N Kemeny ◽  
W E Enker ◽  
D P Kelsen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lower Incidence ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
High Dose ◽  
Preoperative Radiation ◽  
Unresectable Disease ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

PURPOSE To determine if fluorouracil (5-FU) plus high-dose leucovorin (LV) enhances local response in patients receiving preoperative radiation therapy (RT) for adenocarcinoma of the rectum, we compared the degree of downstaging in patients receiving preoperative RT with or without chemotherapy. PATIENTS AND METHODS For this comparison, three groups of patients who were treated with identical doses and techniques of preoperative pelvic RT (total dose of 5,040 cGy) were examined. Group 1 included 20 patients with unresectable disease who received combined RT and LV/5-FU. Group 2 included 11 patients with unresectable disease who received preoperative RT. Group 3 included 21 patients with invasive, resectable, primary disease who received preoperative RT. RESULTS Patients with unresectable disease who received LV/5-FU had a higher rate of pathologic complete response (20% v 0%) and a lower incidence of positive nodes (30% v 64%) compared with those who did not receive chemotherapy. Even when the most favorable group of patients was included (group 3), patients who received LV/5-FU still had a higher complete response rate (20% v 6%) and a lower incidence of positive nodes (30% v 53%) compared with those who received RT without LV/5-FU. Of those patients with initially unresectable disease, the resectability rate was higher in those who received LV/5-FU compared with those who did not receive LV/5-FU (90% v 64%). Patients who received LV/5-FU experienced slightly more grade 1 to 2 fatigue, stomatitis, nausea, and grade 3 diarrhea, tenesmus, and dysuria. CONCLUSIONS Despite the fact that patients who received chemotherapy (group 1) had more advanced disease compared with those with resectable disease (group 3), the addition of LV/5-FU increased the resectability and downstaging rates. The ultimate impact of a complete response as well as a decrease in the incidence of pelvic nodes on local control and survival remains to be determined. However, given the enhancement of down-staging in patients with unresectable rectal cancer, we are encouraged by the combined modality approach.

Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery 

1999 ◽  
Vol 90 (5) ◽  
pp. 1354-1362 ◽  
Author(s):  
Marc De Kock ◽  
Philippe Gautier ◽  
Athanassia Pavlopoulou ◽  
Marc Jonniaux ◽  
Patricia Lavand'homme
Keyword(s):  
High Dose ◽  
General Anesthetics ◽  
Visual Analogue Pain ◽  
Pain Scores ◽  
Arterial Blood ◽  
Sedation Scores ◽  
Group 3 ◽  
Group 2 ◽  
High Doses ◽  
Group 1

Background The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Methods Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. Results During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Conclusion Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.

scholarly journals Efficacy of Chemotherapy or Chemo-Anti-PD-1 Combination after Unsatisfactory Response of Anti-PD-1 Therapy for Relapsed and Refractory Hodgkin Lymphoma: A Retrospective Series from Lysa Centers

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 652-652
Author(s):  
Cédric Rossi ◽  
Julia Gilhodes ◽  
Marie Maerevoet ◽  
Charles Herbaux ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Complete Response ◽  
High Rate ◽  
High Dose ◽  
Group 2 ◽  
Group 1

Abstract Introduction: Hodgkin lymphoma (HL) pts who relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV) therapy have a poor outcome. For these relapsed and refractory (R/R) HL pts, anti-PD-1 therapy gives a high rate of objective responses. However, the rate of complete response (CR) remains modest and in the updated results of anti-PD-1 therapy clinical trials, about 50% of pts are still without progressive disease after one year of treatment. As anti-PD-1 therapy modifies the anticancer immune response, we hypothesize that anti-PD-1 therapy may increase sensitivity to chemotherapy (CT) given after anti-PD-1 therapy (sequential strategy) or in combination with anti-PD-1 therapy after an unsatisfactory response to immunotherapy (concomitant strategy). We retrospectively analyzed these two clinical situations in 30 R/R HL pts from LYSA centers treated with anti-PD-1 therapy. Methods: We included R/R HL pts from 14 LYSA centers who received anti-PD-1 therapy in the context of clinical trials (N=4) or an authorization for temporary use (ATU) from the French medical drug agency (N=26). Before the anti-PD-1 therapy, pts had received a median of six (range, 2-14) lines of therapy, 69% had HDT+ASCT, 14% had allograft and 93% had been treated with BV. We considered two groups of pts: i. 19 pts (63%) in whom the anti-PD-1 therapy was stopped at the introduction of CT (Group 1); ii. 11 pts (37%) with an unsatisfactory response to anti-PD-1 therapy in whom a combination of CT with immunotherapy was initiated to optimize the response (Group 2). The quality of the response after the introduction of CT was evaluated retrospectively by each treating physicians according to Cheson 2007 or 2014 criteria. We also determined whether new CT treatments after and in combination with anti-PD-1 therapy led to unexpected toxicities and whether new treatment schedules made pts eligible for allograft. Results: At the start of anti-PD-1, the median age of pts was 37 years old (range, 20-75), 24% had Ann Arbor III/IV stages, 34% had B symptoms and 21% had a performance status (PS) of 2-3. Patients received a median of 10 infusions (range, 2-52) of anti-PD-1 therapy with nivolumab (N=26, 87%) or pembrolizumab (N=4, 13%). The best responses achieved during anti-PD-1 therapy were a complete response (CR) for 5 patients, a partial response (PR) for 17 pts, stable disease (SD) for 2 pts and progression for 6 pts. In group 1, 17 pts were in progression, one pt in PR, and another pt in SD at the end of anti-PD-1 therapy alone. In group 1, after anti-PD-1 therapy, the pts were treated with vinblastine (N=3), gemcitabine (N=2) or bendamustine alone (N=3) or in combination with BV (N=4), GVD (N=1), ICE (N=1), DHAP (N=1), escalated BEACOPP (N=1), vinorelbine (N=1), vepeside (N=1) and caelyx (N=1). In group 2, before the combination, the response status was progression for 7 pts and PR for 4 pts. In group 2, to optimize the response to anti-PD-1, pts received vinblastine (N=7), gemcitabine (N=2) and BV (N=2). In the 28 evaluable pts, 11/18 (61%) in group 1 and 9/10 (90%) in group 2 showed an improved response after chemotherapy alone or combination with anti-PD-1 therapy respectively. In group 1, there were 6 CR (32%), 5 PR (26%), 1 SD (5%) and 6 PD (32%) (Figure 1B). In group 2, there were 5 CR (45%), 5 PR (45%) and 1 SD (10%) (Figure 1A). Of note, among the ten pts treated with vinblastine, 4 were in CR, 3 in RP, 1 in SD and 2 in progression. No unexpected toxicity was observed during the CT. Four pts had an allograft after the sequential CT (N=3) and concomitant CT strategy (N=1). Three pts were in CR 274, 279 and 480 days after the allograft and the fourth has not yet been evaluated. Allografts are now scheduled for 6 pts. With a median follow-up of 9.1 months (95%CI, 6.1-14) following the initiation of chemotherapy (alone or combined) the median PFS and OS were 8.4 and 14.6 months, respectively. Conclusions: Our retrospective study showed that pts with an unsatisfactory response or PD with anti-PD-1 therapy had a new objective response with CT alone (61%) or CT in combination with anti-PD-1 therapy (90%). This response could make some pts eligible for allograft. Prospective clinical trials are needed to confirm the synergistic effect of CT with anti-PD-1 therapy and to determine which CT provides the best results in combination with these checkpoint inhibitors. Figure 1 Figure 1. Disclosures Ysebaert: Janssen: Consultancy, Research Funding, Speakers Bureau. Ghesquières: Celgene and Mundipharma: Consultancy, Honoraria; Roche: Research Funding.

High-dose lidocaine does not affect defibrillation efficacy: implications for defibrillation mechanisms

1998 ◽  
Vol 274 (4) ◽  
pp. H1113-H1120 ◽  
Author(s):  
Michael R. Ujhelyi ◽  
J. Jason Sims ◽  
Allison Winecoff Miller
Keyword(s):  
Ventricular Fibrillation ◽  
Cycle Length ◽  
Low Dose ◽  
High Dose ◽  
Channel Blockade ◽  
Group 3 ◽  
Baseline Values ◽  
Group 2 ◽  
Very High ◽  
Group 1

This study assessed the effect of low (10 mg ⋅ kg−1 ⋅ h−1) and very high (18 mg ⋅ kg−1 ⋅ h−1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 ( n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 ( n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% ( P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values ( P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 ± 2.7 to 12.9 ± 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation ( P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values. However, there is a possibility that an unidentified action of lidocaine is responsible for these effects.

Evaluation of the Impact of Three Different Pre-Transplant Strategies On the Outcome of Myeloma Patients Candidates to High-Dose Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1223-1223
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Luciana Barbarano ◽  
Annalisa Citro ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Patient Flow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Oral Dexamethasone ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p<0.00001). The number of responsive pts progressively increased from 87% after Vel-Dex (CR 31%), to 96% after transplant (CR 38%). Response rates of group 1 and 2 patients were not significantly different either after induction (p=0.6), after DCEP (p=0.5), and after Tx (p=0.65). On intention to treat basis, vel-dex induction produced a better, although not significant, PFS (34.6 months vs 29 in group 1 and 26.8 in group 2, p=0.56). OS were not statistically different among the three groups, event though the different follow-up could affect the analysis (median OS 110 in group 1, 66 months in group 2, and not reached in group 3, p=0.37). In multivariate analysis PFS was improved only by the achievement of CR (p=0.001). No significant difference was observed between VGPR or PR (p=0.43). Conclusion In this study, only CR not VGPR impacts on the outcome. Vel-Dex producing a significant high CR rate after TX (38%), seems to improve survival of MM patients candidate to high-dose therapy with respect to conventional pre-transplant strategies. Disclosures Morra: Roche:.

scholarly journals High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 610-616 ◽  
Author(s):  
MR Bishop ◽  
JR Anderson ◽  
JD Jackson ◽  
PJ Bierman ◽  
EC Reed ◽  
...  
Keyword(s):  
High Dose Chemotherapy ◽  
High Dose ◽  
Continuous Intravenous Infusion ◽  
Colony Stimulating Factor ◽  
Group 3 ◽  
Macrophage Colony Stimulating Factor ◽  
Group 2 ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Group 1

Between June 1989 and June 1992, 144 patients participated in sequential clinical trials using peripheral blood progenitor cells (PBC) as their sole source of hematopoietic rescue following high-dose chemotherapy. All patients had received prior extensive combination chemotherapy and had marrow defects that precluded autologous bone marrow transplantation (ABMT). PBC were collected according to a single apheresis protocol. The initial 86 patients (group 1) had PBC collected without mobilization. Beginning in April 1991, PBC were mobilized solely with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Thirty-four patients (group 2) received rHuGM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion, and 24 patients (group 3) received rHuGM-CSF at a dose of 250 micrograms/m2/d by continuous intravenous infusion. Patients underwent at least six aphereses and had a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg collected. Cytokines were not routinely administered immediately after transplantation. A median of nine aphereses were required to collect PBC in group 1 and seven aphereses for groups 2 and 3 (P = .03). The time required to recover 0.5 x 10(9)/L granulocytes after transplant was significantly shorter (P = .0004) for the mobilized groups; the median time to recovery was 26 days for group 1, 23 days for group 2, and 18 days for group 3. Transplantation of PBC mobilized with rHuGM-CSF resulted in a shorter time to platelet (P = .04) and red blood cell (P = .01) transfusion independence. Mobilization with rHuGM-CSF alone resulted in efficient collection of PBC, that provided rapid and sustained restoration of hematopoietic function following high-dose chemotherapy. Mobilization of PBC with rHuGM-CSF alone is an effective method for patients who have received prior chemotherapy and have bone marrow abnormalities.

scholarly journals Effects of Aqueous Colocasia esculenta Extracts on Selected Biochemical Parameters in Phenyl Hydrazine Induced Male Anemic Albino Rats

2020 ◽  
pp. 13-23
Author(s):  
Adekunle Abiodun Ayoade ◽  
Adedayo Emmanuel Ogunware ◽  
Ifeoluwa Israel Odekunle ◽  
Pelumi Abimbola Adedigba
Keyword(s):  
Plant Extract ◽  
Total Protein ◽  
Low Dose ◽  
Colocasia Esculenta ◽  
High Dose ◽  
Phenyl Hydrazine ◽  
Group 3 ◽  
Group 2 ◽  
Protein Serum ◽  
Group 1

Aims: In this study, the effect of Colocasia esculenta a hematinic plant on biochemical parameters levels (Direct, Total and unconjugated bilirubin, creatinine, total protein, serum albumin and urea) was assessed to determine if the plant extract can reverse the abnormality in the values of these parameter. Methodology: The experimental animals were divided into four groups as follows; group 1(non-anemic control), group 2 (anemic untreated), group 3 (anemic treated with low dose of plant extract 100 mg/ml), group 4 (anemic treated with high dose of plant extract 500 mg/ml). Anemia was induced in group 1, group 2 and group 3 with 60 mg/kg of phenyl hydrazine for 2 days. After induction of anemia group 2 and group 3 was treated with 100 mg/kg and 500 mg/kg of plant extract for 7 days. After 7-day blood sample was collected through heart puncture and centrifuged for serum. Then, Bilirubin, creatinine, total protein, serum albumin and urea test were carried out. Results: The anemic untreated group had the highest bilirubin, creatinine and urea value of 1.3 mg/dl, 3.97 mg/dl and 71.78 g/l respectively compared to the non-anemic control (bilirubin-0.4 mg/dl, creatinine-3.13 mg/dl and urea 60.35 mg/dl), anemic treated with low dose (bilirubin-0.37 mg/dl,creatinine-1.40 mg/dl and urea-41.82), and anemic treated with high dose (bilirubin-0.25 mg/dl, creatinine-0.86 mg/dl, and urea-48.66 mg/dl) with significant increase in phenyl hydrazine value at p<0.05 .The anemic nontreated group experienced a reduced value of total protein and albumin of 49.78 g/l and 24.46 g/l respectively compared to the non-anemic control (total protein-66.2 g/l and albumin-37.67 g/l) ,anemic treated with low dose (total protein-67.5 g/l and albumin-19.2 g/l), and anemic treated with high dose (total protein-21.9 g/l and albumin-81.6 g/l). Conclusion: The obtained results from this study revealed the anti-anemia potentials of aqueous extracts of Colocasia esculenta.

scholarly journals Therapeutic efficacy of low dose (Dhaka regimen) versus high dose (Pritchard regimen) magnesium sulphate for management of eclampsia and impending eclampsia

2018 ◽  
Vol 7 (6) ◽  
pp. 2333
Author(s):  
Nisha Bhagat ◽  
Preet Kamal Bedi ◽  
Davinder Pal ◽  
Arunima Saini
Keyword(s):  
Side Effects ◽  
Magnesium Sulphate ◽  
Lower Incidence ◽  
Therapeutic Efficacy ◽  
Low Dose ◽  
Secondary Outcome ◽  
High Dose ◽  
Common Diagnosis ◽  
Group 2 ◽  
Group 1

Background: To compare the efficacy of low dose (Dhaka regimen) vis-a vis high dose (Pritchard regimen) magnesium sulphate in management of eclampsia and impending eclampsia.Methods: The open-label, comparative study was conducted on 90 pregnant patients. They were admitted to emergency Department of Obstetrics and Gynaecology, Government Medical College, Amritsar with eclampsia or impending eclampsia. 10 patients dropped out at various stages of study and finally, 80 were enrolled and randomized (1:1 ratio) into two groups. Group-1, N=40 were given low dose MgSO4 (Dhaka regime) and Group-2, N=40 were given high dose MgSO4 (Pritchard). Termination of pregnancy was done as per Bishop’s score, gestation age, maternal and fetal status. Primary outcome measure was therapeutic efficacy of equivalence for control of seizures whereas secondary outcome was adverse side-effects of both the regimens.Results: Mean age in Group-1 was 24.90±4.02 years and that of Group-2 was 25.67±3.79 years. Antepartum eclampsia was the most common diagnosis among groups i.e., 47.5% and 55% respectively. After treatment, the seizure control was 97.5% in Group-1 and 100% in Group-2 with comparable results (𝑥2=1.013; p=0.314). However, highly significant difference was observed among dosage of MgSO4 that was required for control of seizure (23.75±2.71 gm versus 41.35±4.76 gm; p<0.001). Group-1 showed lower incidence of side-effects that is, loss of deep tendon reflex as compared to Group-2, but neonatal outcomes were comparable in both groups.Conclusions: Low dose (Dhaka regimen) was equally effective in control of seizures as compared to high dose (Pritchard regimen) with lower incidence of side-effects.

Anti-GD2 monoclonal antibody 3F8 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) for primary refractory neuroblastoma (NB) in bone marrow (BM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9502-9502 ◽  
Author(s):  
B. H. Kushner ◽  
K. Kramer ◽  
S. Modak ◽  
N. V. Cheung
Keyword(s):  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Post Transplant ◽  
Gm Csf ◽  
Group 3 ◽  
Macrophage Colony Stimulating Factor ◽  
Group 2 ◽  
Macrophage Colony

9502 Background: Despite high-dose chemotherapy, NB in BM often persists and forebodes death. Methods: 3F8/GM- CSF was used in 63 patients (pts) with NB in BM by morphology and/or metaiodobenzylguanidine (MIBG) scan, no prior progressive disease or immunotherapy, and no soft tissue NB; 35 (56%) of the pts had received second-line therapy and 24 (38%) were post-transplant. Treatment was repeated if human anti-mouse antibody (HAMA) titer was low. Results: Of 30 pts with NB in BM but normal MIBG scans (Group 1), 25 (83%) had complete response (CR) after cycle 1 (n=17), cycle 2 (n=5), or cycle 3, 6, or 7 (one pt each), including 13/16 post-transplant pts. Among 15 pts with NB in BM and abnormal MIBG scans (Group 2), 12 (80%) had CR in BM after cycle 1 (n=5), cycle 2 (n=4), cycle 4 (n=2), or cycle 9 (n=1); MIBG scans normalized in 5/11 pts who had multiple abnormal MIBG(+) sites and in 4/4 pts who had one abnormal MIBG(+) site (irradiated in three pts). Of 18 pts who had abnormal MIBG scans but no NB seen in BM tests (Group 3), 14 (78%) had CR or near CR, including eight whose MIBG(+) sites were irradiated. Early HAMA limited treatment in 19 pts, but was prevented by high-dose cyclophosphamide. CR continues in 12 pts (five never transplanted) with long follow-up (20+ -to- 146+ months) and in 10 pts with short follow-up. The only common toxicities of this outpatient treatment were pain and hives; there were no long-term toxicities. Conclusions: 3F8/GM-CSF is well tolerated, achieves a high CR rate against primary refractory NB in BM (including post-transplant), and may prolong disease control in non- transplanted pts. Further experience will show whether it ought to be used for consolidative therapy in place of myeloablative cytoreduction. No significant financial relationships to disclose.

Alternative therapeutic approaches after induction chemotherapy for tonsil squamous cell carcinomas

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17010-e17010
Author(s):  
F. Huguet ◽  
M. Gratacap ◽  
J. Ménard ◽  
S. Perie ◽  
B. Angelard ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Predictive Factor ◽  
Survival Rates ◽  
Complete Response ◽  
Squamous Cell Carcinomas ◽  
Pathological Response ◽  
Primary Site ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

e17010 Background: The role of induction chemotherapy (ICT) in the treatment of head and neck squamous cell carcinomas (SCC) remains controversial. This retrospective study aims to evaluate the outcome of patients with tonsil SCC treated with ICT followed by surgery and/or external beam radiotherapy (EBRT). Methods: Between 1997 and 2007, 103 patients (pts) with tonsil SCC received an ICT in Tenon Hospital. Most of pts (88%) received cisplatin (25 mg/m2) and 5-fluorouracil (1,000 mg/m2) for 4 days with a mean of 2.5 cycles. After ICT, 85 pts were operated. After surgery, 69 pts received a dose of 50 to 70 Gy on the primary site depending on pathological findings (Group 1). Sixteen pts with negative margins and no lymph node metastasis didn't receive any EBRT (Group 2). The remaining 17 pts were treated by EBRT without surgery (Group 3). The mean follow-up was 38 months. Results: No significant difference appears between our different groups except for the TNM stage and the tumour pathological response to ICT. After ICT, pathological complete response was observed in 18 pts (25%) for the primary site and 20 pts (34%) for lymph nodes. Clinical and radiological assessment of response after ICT was not predictive of the pathological response. The TNM stage was the only predictive factor for complete response. The 5-year disease-free survival rates were 68% for the whole population, 73% for the Group 1, 43% for the Group 2, 68% for the Group 3 (p = 0.5). A poor pathological response after ICT was the single independent predictive factor of tumour relapse (p = 0.04). In the Group 2, 6 pts had a relapse, among them 4 had EBRT in a second time. The 5-year specific survival rates were 78% for the whole population, 76% for the Group 1, 76% for the Group 2, 39% for the Group 3 (p = 0.03). The radio-clinical evaluation of response, the surgery and the pathological response were predictive factors of specific survival. Conclusions: Pts with a complete pathological response after ICT who were not irradiated had a non significant increase of the relapse rate with a specific survival identical to the group of irradiated pts. This data have to be confirmed by a prospective trial. No significant financial relationships to disclose.

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