Chemotherapy alone in laryngeal squamous cell carcinoma.

AIMS: To evaluate the results of chemotherapy alone in patients with invasive squamous cell carcinoma of the larynx who have achieved a complete clinical response after an induction chemotherapy protocol. METHODS: A comparison of results in a group of complete responders managed with a chemotherapy alone protocol, matched with those of an incomplete responder group managed with conventional modalities. RESULTS: The survival rate of the complete responder group was significantly higher than that of the incomplete responder group. No statistically significant difference was noted between the two groups in terms of local failure and nodal recurrence. CONCLUSION: Our results confirm the fact that chemotherapy alone is a viable option in selected patients with carcinoma of the larynx who have achieved a complete clinical response after an induction chemotherapy protocol. This therapeutic approach allows surgery and/or radiation therapy to be reserved for the management of metachronous second primary tumours.

Catheter-related upper extremity deep venous thrombosis in cancer patients: a prospective study based on Doppler US.

PURPOSE: This prospective study extending for more than 3 years had two objectives: (a) to use Doppler ultrasonography (US) to estimate the incidence of asymptomatic catheter-related upper extremity deep venous thrombosis (DVT) in a large population and (b) to study the effect of the catheter position as an individual risk factor for catheter-related DVT. MATERIALS AND METHODS: Between October 1995 and June 1998, a total of 145 patients who had oropharyngeal tract cancer and who were fitted with the same totally implantable central venous catheters (CVCs) were included in the study. Follow-up included (a) estimation of the position of each catheter tip on a chest radiograph obtained immediately after surgery and (b) regular monthly Doppler US screening for catheter-related DVT. RESULTS: Seventeen patients developed catheter-related DVT; 13 of them were asymptomatic. The mean interval between CVC implantation and detection of thrombosis was 42.2 days. Correct positioning of the distal catheter tip was associated with a significantly lower rate of catheter-related DVT. Only five of 87 patients with a correctly positioned distal catheter tip (ie, either in the superior vena cava or at the junction between the right atrium and the superior vena cava) developed thrombosis, compared with 12 of 26 patients with a misplaced catheter (P <.001). The side on which the CVC was implanted did not influence the catheter-related DVT rate. CONCLUSION: The rate of asymptomatic catheter-related DVT is high and could be lowered with correct initial CVC positioning.

Phase I-II study of irinotecan in combination with mitomycin C in patients with advanced gastrointestinal cancer.

This phase I-II study was conducted to determine the maximum tolerated dose and optimal schedule of a combination of irinotecan (CPT 11) and mitomycin C (MMC) in a population of previously treated patients with gastrointestinal malignancies. Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2. All treatment was repeated at 21-day intervals. The dose-limiting toxicity was hematologic (thrombocytopenia at level 4), and the recommended doses for subsequent phase II studies are MMC 8 mg/m2 with irinotecan 325 mg/m2. Evidence of efficacy was seen at all dose levels examined and justifies further exploration of this combination in a less heavily pretreated patient population.

Chemotherapy combined with conservation surgery in the treatment of early larynx cancer.

In the past 20 years, strategies based on the use of platinum-based induction chemotherapy regimens have been developed in an attempt to preserve the larynx, increase local control, and improve survival in patients with advanced laryngeal cancer. In patients with early-stage laryngeal cancer, it is commonly thought that there is no role for induction chemotherapy. In this review, we support the notion that there is growing evidence available in the literature documenting the need and the role for induction chemotherapy as well as the need and the role for the use of conservation laryngeal surgery after induction chemotherapy in early-stage laryngeal cancer (T1-2N0).

A multimodal strategy for the treatment of patients with T2 invasive squamous cell carcinoma of the glottis.

BACKGROUND: The current conservative standard of care for T2 squamous cell carcinoma of the glottis is either partial laryngectomy or radiation therapy. METHODS: Based on an inception cohort of 100 patients with T2 squamous cell carcinoma of the glottis and a minimum of 3 years of follow-up, the present study documented the results achieved with a multimodal strategy using platinum-based induction chemotherapy and partial laryngeal surgery. Statistical analysis of survival and local control was based on the Kaplan-Meier actuarial life table method. Univariate analysis was performed to determine whether there was a correlation among various factors and toxicity, clinical response, histologic regression, local control, and survival. RESULTS: A complete clinical response and a partial response after induction chemotherapy was achieved in 24% and 58% of patients, respectively. Complete histologic regression was noted in 31%. A significant statistical relation (P < 0.0001) was noted between a complete clinical response after induction chemotherapy and a complete histologic regression. The 5-year actuarial survival estimate was 85.8%. The 5-year actuarial local control estimate was 95.7% (97.7% if the vocal cord was mobile and 93.8% if the motion of the vocal cord was impaired). Salvage treatment resulted in an overall 99% rate of local control and a 95% rate of laryngeal preservation. CONCLUSIONS: Because this represents a nonrandomized retrospective study, no definitive conclusions can be derived. However, when compared with the data reported in a large series using radiation therapy or partial laryngectomy alone, this 10-year experience suggests that, in patients with "early" invasive squamous cell carcinoma of the glottis, the use of platinum-based induction chemotherapy prior to a conventional conservative treatment modality should be investigated further.

Cisplatin-fluorouracil exclusive chemotherapy for T1-T3N0 glottic squamous cell carcinoma complete clinical responders: five-year results.

PURPOSE: To evaluate cisplatin-fluorouracil exclusive chemotherapy (EC) for T1-T3N0 glottic squamous cell carcinoma complete clinical responders (CCR) after cisplatin-fluorouracil induction chemotherapy (IC). PATIENTS AND METHODS: A retrospective analysis was performed of 58 patients with T1-T3N0 glottic squamous cell carcinoma CCR after IC consecutively managed at our department between 1985 and 1992. Twenty-one CCR were managed with EC. Thirty-seven CCR were managed with IC and a conventional laryngeal-preservation modality. Analyses of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor were performed using the Kaplan-Meier actuarial life-table method. In CCR managed with EC, the independent factors of age, tumor classification, exact tumor location, true vocal cord motion, arytenoid cartilage motion, total dosage of drugs delivered, and number of courses received were tested for potential correlation with survival, local recurrence, nodal recurence, and distant metastasis. RESULTS: The 5-year survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor rates in CCR managed with EC were 95.2%, 70.7%, 0%, 0%, and 14.3%, respectively. The 5-year rates of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor in CCR managed with IC and a conventional laryngeal-preservation modality were 86.1%, 97%, 2.7%, 6%, and 14.5%, respectively. Local recurrence was statistically more likely in CCR managed with EC (P = .002). Local recurrence in CCR managed with EC was always salvaged with partial laryngectomy or radiation therapy, which resulted in an overall 100% local control and laryngeal-preservation rate within this group. In CCR managed with EC, none of the variables analyzed was statistically related to survival, local recurrence, nodal recurrence, or distant metastasis. CONCLUSION: The present retrospective studies demonstrated that within T1-T3N0 glottic squamous cell carcinoma CCR, there is clearly a significant subset of patients with chemocurable tumors who achieved both perfect preservation of structure-supporting voice and long-term survival after EC. Careful monthly follow-up evaluation allowed for timely successful salvage of local recurrence after EC without the need for total laryngectomy. Such management did not appear to increase the risk for subsequent nodal failure, subsequent distant metastasis, or reduced survival.

Cisplatin-based neoadjuvant chemotherapy and combined resection for ethmoid sinus adenocarcinoma reaching and/or invading the skull base.

OBJECTIVE: To review our experience with cisplatin-based neoadjuvant chemotherapy before en bloc resection via a combined neurosurgical and transfacial approach for ethmoid sinus adenocarcinoma reaching and/or invading the skull base. DESIGN: Case series. SETTING: A tertiary care center and university teaching hospital. PATIENTS: Twenty-two patients with primary untreated ethmoid sinus adenocarcinoma reaching and/or invading the skull base consecutively treated between 1984 and 1992 with cisplatin-based neoadjuvant chemotherapy and combined neurosurgical and transfacial approach. MAIN OUTCOME MEASURES: Statistical analysis of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor incidence based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors, survival, and local recurrence. Clinical response, histological response, toxic effects of chemotherapy, and postoperative course were also reported. RESULTS: The Kaplan-Meier 3-year survival, local control, nodal recurrence, and distant metastasis estimates were 68.1%, 65.7%, 5.3%, and 10%, respectively. Metachronous second primary tumor was not encountered in our series. Survival was statistically more likely to be reduced in patients with intrasphenoidal tumor extent (P = .04) and local recurrence (P = .01). Local recurrence was statistically more likely in patients with intrasphenoidal tumor extent (P = .002) and no response to cisplatin-based neoadjuvant chemotherapy (P = .03). CONCLUSIONS: The results achieved suggest that cisplatin-based neoadjuvant chemotherapy before combined neurosurgical and transfacial approach should be further investigated for the treatment of ethmoid sinus adenocarcinoma reaching and/or invading the skull base.

[Prospective study of thromboses of the subclavian vein after setting implantable venous access systems in cervico-facial cancerology]. / Etude prospective des thromboses de la veine sous-clavière après mise en place d'un système d'accès veineux implantable en cancérologie cervico-faciale.

Seventy-eight consecutive patients treated by chemotherapy for ENT cancers and having a subclavian catheter for venous access were studied prospectively to assess the prevalence of venous thrombosis. Thrombosis of the subclavian vein was demonstrated clinically in 4 patients and by ultrasonography in 7 patients. The prevalence of thrombosis was 14.1%. No clinical or biological predisposition factor could be identified. Subclavian thrombosis mostly occurred during the second month after implantation (91% of cases). Ultrasonography seems the most useful non-invasive technique for the diagnosis of subclavian thrombosis.

[Exclusive chemotherapy in T1-T3N0 cancers of the vocal cord with complete clinical response after neoadjuvant treatment with a cisplatin-fluorouracil combination]. / Chimiothérapie exclusive dans les cancers de la corde vocale T1-T3N0 en réponse clinique complète après traitement néo-adjuvant cisplatine-fluorouracile.

OBJECTIVES: Evaluation of cisplatin-fluorouracil exclusive chemotherapy for invasive squamous cell carcinoma of the glottis staged as T1-T3N0 with a complete response after cisplatin-fluorouracil neo-adjuvant chemotherapy. METHODS: A retrospective analysis of the files of 69 patients with a well-differentiated untreated invasive squamous cell carcinoma, staged as T1-T3N0 with a complete response after cisplatin-fluorouracil neo-adjuvant chemotherapy is presented. Actuarial analysis (Kaplan Meier method) of survival and local failure is presented among the group of 25 patients treated with exclusive chemotherapy and the group of 44 patients in whom the local treatment (partial laryngeal surgery or radiation therapy) initially planned was maintained. RESULTS: Three-year survival and local control estimate was 91.8% and 69.3%, respectively after exclusive chemotherapy and 92.5% and 97.2% if the local treatment was performed as initially planned. Patients with local recurrence after exclusive chemotherapy were always salvaged with partial laryngeal surgery or radiation therapy resulting in an overall 100% local control and laryngeal preservation rate. CONCLUSION: Exclusive chemotherapy for T1-T3N0 glottic carcinomas with a complete response after cisplatin-fluorouracil neo-adjuvant chemotherapy should be considered especially in patients in whom preservation of voice is of utmost importance.

A clinical trial of continuous cisplatin-fluorouracil induction chemotherapy and supracricoid partial laryngectomy for glottic carcinoma classified as T2.

BACKGROUND: Vertical partial laryngectomy (VPL) and radiation therapy (RT) are the recommended conventional conservative options for glottic carcinoma classified as T2. In series presenting more than 100 patients with a minimum 3-year follow-up, however, local recurrence rates were reported as 22-43.5%. The authors' experience with a new strategy based on continuous cisplatin-fluorouracil induction chemotherapy (IC) and supracricoid partial laryngectomy with cricohyoepiglottopexy (CHEP) is presented. METHODS: A retrospective analysis of 67 patients who presented with untreated moderately to well differentiated invasive glottic carcinoma classified as T2, managed from 1983 to 1991 with IC and CHEP, was conducted. Statistical analysis of survival, local control, nodal control, distant metastasis, and metachronous second primary tumor incidence was based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors and survival, local recurrence, and nodal recurrence. Clinical response, histologic response, IC toxicity and postoperative course were reported. RESULTS: The Kaplan-Meier 5-year survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate were 92.3%, 5.6%, 1.5%, 1.8%, and 5.6%, respectively. Overall laryngeal preservation was achieved in 65 patients (97%). Ultimate local control was achieved in all patients but one. Nodal recurrence was statistically more likely in patients presenting with a local recurrence. Analysis of the specimens demonstrated complete histologic response to IC in 25 (37.3%) patients. A strong statistical relation (P < 0.0001) was noted between complete clinical response after IC and complete histologic response. CONCLUSIONS: The change from the prevailing treatment modalities of RT and VPL to a new multimodal strategy (IC+CHEP) did not decrease survival and allowed for an increase in laryngeal preservation rate. The high rate (37.3%) of complete histologic response suggests that IC deserves further consideration in the management of patients with glottic carcinoma classified as T2. The favorable results achieved in this series, when compared with historic controls, should stimulate prospective clinical trials comparing the two surgical procedures (CHEP vs. VPL with or without IC) for resection of Stage II glottic carcinoma.

[Cervicofacial cancerology: complications of implantable systems of venous access. Prospective study]. / Cancérologie cervico-faciale: complications des systèmes d'accès veineux implantables. Etude prospective.

OBJECTIVE: Implantable systems for venous access are widely used in cervicofacial cancer. We prospectively evaluated complications related to this type of venous access in our cancer patients. METHODS: From September 1991 to September 1993, an implantable system for venous access was installed in 164 patients with epidermoid carcinoma of the upper respiratory and digestive tracts. The systems were implanted in the subclavian vein by 20 different operators (mean number of implants per operator = 8.2). All catheters were tunnelized. Chemotherapy was a combination of 5 fluorouracil and cisplatinum. RESULTS: Immediate complications included impossible implantation (n = 12, 7.3%), pneumothorax (n = 5), false passage (n = 4), haematoma (n = 3), arterial puncture (n = 2) and abscess of the thoracic wall (n = 1). During use, complications included extravasation (n = 4), catheter thrombosis (n = 2), venous thrombosis (n = 2) and infection at the site of implantation, desinsertion of the catheter from the chamber, haematoma at the site of implantation and septicaemia (n = 1 each). The rate of complications was related to implantation (17% of the implantations) or to use (8%). CONCLUSIONS: The rate of complications due to implantable venous access systems is relatively low, suggesting that these systems are acceptable for ambulatory chemotherapy.

[Cisplatin-fluorouracil chemotherapy in epidermoid cancers of glottic origin staged as T2]. / Chimiothérapie cisplatine-fluorouracile dans les cancers epidermoides à point de départ glottique classes T2.

A retrospective analysis of 94 patients presenting well-differentiated untreated invasive glottic squamous cell carcinomas, staged as T2 according to the 1987 Union Internationale contre le Cancer staging classification system, managed at our institution from March 1982 to April 1991 with cisplatin-fluorouracil neo-adjuvant chemotherapy, was conducted. Following neo-adjuvant chemotherapy, partial laryngeal surgery, and radiation therapy were performed in 85.1% (80/94) and 4.2% (3/94) of cases, respectively. Perioperative chemotherapy (fluorouracil) and postoperative chemotherapy (cisplatin-fluorouracil) was performed in 68.7% (55/80) and 63.7% (51/80) of patients who underwent surgery, respectively. Following neoadjuvant chemotherapy, one patient (1.1%) refused any form of treatment, and "exclusive" chemotherapy was performed in 9.6% (9/94) of cases. A 3-year follow-up was always achieved and 66 patients (70.2%) presented with a 5-year follow-up. A complete clinical response was achieved in 32.9% of cases following neo-adjuvant chemotherapy. A complete histological response was noted in 31.2% (25/80) of patients treated with partial laryngeal surgery following neo-adjuvant chemotherapy. A strong statistical relation was noted between complete clinical response and complete histological response (p < .0001). Chemotherapy related death never occurred in our series however chemotherapy related toxicity lead to reduction in the drug dosages and chemotherapy arrest in 14.3% and 3.6% of cases, respectively. The Kaplan-Meier 5-year survival, local recurrence, nodal recurrence, distant metastasis, and second primary estimate was 84.9%, 8.4%, 1.1%, 2.2%, and 10%, respectively. The overall local recurrence rate varied from 25% following neo-adjuvant chemotherapy and radiotherapy, to 33.3% following "exclusive" chemotherapy, and 3.7% following neo-adjuvant chemotherapy and partial laryngeal surgery. Overall local control and laryngeal preservation was achieved in 98.9% and 97.8% of patients respectively. Our data suggests that the use of neo-adjuvant cisplatin-fluorouracil induction chemotherapy deserves further consideration in the management of glottic carcinomas staged as T2.

[Conservative surgery of the larynx as an alternative to total laryngectomy after neoadjuvant chemotherapy. Initial results]. / Chirurgie conservatrice du larynx comme alternative a la laryngectomie totale après chimiothérapie néo-adjuvante. Résultats préliminaries.

A retrospective study of 149 squamous cell carcinomas of the larynx and epilarynx in whom a total laryngectomy was initially planned is reported. All the patients were treated by neoadjuvant chemotherapy. After completion of chemotherapy, the initially planned therapeutic protocol was modified in 56 patients (37.6%) in order to preserve the laryngeal physiologic functions. A total laryngectomy was performed in 23 patients (41%), radiation therapy was administered to 14 (25%) patients chemotherapy was prolonged in 15 patients (26.8%) and four deaths were related to chemotherapy toxicity (7.2%). Actuarial survival of patients treated by partial laryngectomy was statistically higher than survivals of patients treated either by radiation therapy or prolonged chemotherapy. After completion of neoadjuvant therapy patients who refused a total laryngectomy had the worst survival of the series. These results suggest that surgery of the residual tumor (partial laryngectomy) after neoadjuvant chemotherapy could be indicated for selected laryngeal carcinoma in whom a total laryngectomy was initially planned.

Clinical evaluation of the CORDIS vascular access port systems: a multicenter study.

Two non-metallic vascular access port systems, the Multipurpose Access Port (MPAP) and Miniport, developed by CORDIS S.A., France, have been evaluated clinically in 78 cancer patients. During the investigational period covering a total experience of 369 treatment cycles and 1,370 infusion days, no cases of infection or septicemia were observed. Serious complications such as drug extravasation and catheter occlusion occurred, although the incidence was relatively low (+/- 1%) when compared with the number of treatment courses (cycles), but in relation to the number of patients included in this study, the procedure-related complication rate was 17.5% for the MPAP and 15.8% for the Miniport. Procedure-related complications can be avoided by proper handling and use of suitable drug combinations to minimize crystallization reactions within the port-catheter systems. The final complication rate (total minus procedure-related) in terms of termination of treatment, i.e. explantation of the port-catheter system was 12.1% for the MPAP and 12.5% for the MINIPORT, which generally confirms the results of other groups. More than 87% of both port-catheter systems were still functional at the end of evaluation.

[Adjuvant chemotherapy in supraglottic epidermoid carcinoma stage T3]. / Chimiothérapie néo-adjuvante dans les carcinomes épidermoïdes supraglottiques classés T3.

92 squamous cell carcinomas of the supraglottic larynx classified as T3 were treated from 1977 through 1987 and retrospectively analyzed. All the patients of this series received chemotherapy as initial treatment (2 cycles). From 1977 through 1981 the combination of Vincristine-Methotrexate-Bleomycin (VMB) was employed; after 1981, the protocol: Cisplatinum-5 FU with or without Bleomycin (CF) was administered instead of VMB. All the patients were then surgically treated on the tumoral site and cervical lymph chains. At 5-year, there was no significative difference between the two chemotherapeutic regimen in term of locoregional recurrences and second primaries. 5-year actuarial survival rate was higher for patients treated with the CF protocol (71%) versus (54%) with the VMB regimen. Systemic metastases occurred less frequently after CF (4.5%) than after VMB (22.4%). These findings suggest that chemotherapy has substantially some activity against microscopic distant metastases.

[Esthesioneuroblastomas. Could a preoperative chemotherapy improve their prognosis?]. / Les esthésioneuroblastomes. Une chimiothérapie pré-opératoire peut-elle en améliorer le pronostic?

The prognosis of malignant tumours of the olfactory epithelium of the nasal vault stays very poor. In the literature, the 5-year actuarial survival rate ranges between 50% and 65%; the 5-year recovery rate is 15% due to the high frequency of locoregional reoccurrences (60%) and metastasis (35-40%). Up to now chemotherapy was suggested as palliative treatment; but as Esthesioneuroblastomas (ETNB) appear to be sensitive to several chemotherapeutic agents (such as CDDP and 5-FU), we have decided to administer, from now on, to all patients harbouring an ETNB, an inductive chemotherapy whatever the staging and eventual diffusion of the tumour. The present paper presents our recent experience, dealing with such lesions: since 1984, 60 tumours of the ethmoid were treated in our department among which 7 ETNB (11.5%). We discuss our results concerning ETNB.

[Early death after chemotherapy via central venous catheterization in tumors of the upper respiratory and digestive tracts]. / Décès précoces après chimiothérapie par cathéter central dans les tumeurs des voies aéro-digestives supérieures.

Between 1987 and 1988, 1 100 patients were treated by continuous, ambulatory chemotherapy. 35 of these patients died within 90 days of the insertion of the catheter. One death would appear to be related to the catheter, 5 deaths (0.5%) were related to the chemotherapy and 29 deaths were related to progression of the malignant disease. The mortality rate associated with ambulatory chemotherapy via a central catheter would appear to be negligible when compared to deaths related to the progression of the malignant disease.

Adenocarcinoma of the ethmoid sinuses. Results of a new protocol based on inductive chemotherapy combined with surgery. Four years experience.

New therapeutic modalities for Ethmoidal Adenocarcinomas are presented. Thirty three patients harbouring such a tumour have been treated during the last four years. Twenty three were included in the following protocol:--the first step consisted in inductive chemotherapy based on a four-day course of continuous cisplatine (CDDP) and 5-fluoro-uracyl (5-FU infusion)--the second step was the tumour removal, which was performed through a combined transfacial and subfrontal approach. A contralateral ethmoidectomy was always performed. The integrity of the sphenoidal sinus was systematically checked. The cranial base was reconstructed with madreporic coral grafts; then a large extra-dural pediculated galea flap was placed onto the anterior base to line the sub-frontal dura. The authors discuss the results of this series of rare tumours.

[Complete tumor remission after chemotherapy. What should be done?]. / Les régressions tumorales complètes après chimiothérapie. Que faire?

When confronted with complete chemotherapy-induced histological/clinical regression of a tumor, should the initial therapeutical strategy be modified? Such situations occur more and more frequently. Additional treatment must be carried out in all instances. Indeed, a correlation between complete clinical and histological regression was demonstrated in 66% of cases by histological examination of surgical specimens. It is doubtless recommended to avoid mutilating surgery and to continue chemotherapy for another year. However, whenever partial surgery had been programmed initially, the same indications and excision limits should be maintained. Combination chemical and surgical treatments yield better local results. Nonetheless, this is not always the case and the patient's tolerance to chemotherapy and background should influence the final decision. Radiotherapy then constitutes a choice alternative.