Extent of thyroid resection and thyroid function after postoperative radiotherapy following total laryngectomy or total pharyngo-laryngo-esophagectomy.

OBJECTIVE: Concurrent chemoradiotherapy (CCRT) is often performed after total pharyngo-laryngo-esophagectomy (TPLE) or total laryngectomy (TL). Hypothyroidism is one of the side-effects of CCRT. The objective of this study was to ascertain the timing of onset and severity of latent hypothyroidism among patients who underwent radiotherapy (RT) or CCRT after TPLE or TL, using thyroid-stimulating hormone (TSH) as a biomarker, and to explore methods of preventing its development. METHODS: Participants comprised 21 patients who underwent these treatments at Tokyo Medical University Hachioji Medical Center between May 2009 and December 2013. TSH, free thyroxine 3, and free thyroxine 4 levels were used as indicators of thyroid function, and thyroid hormone was administered for TSH levels ≥15 µU/mL. RESULTS: Post-radiotherapeutic TSH levels in 17 of the 21 patients (81%) were not within the reference value, and 10 (48%) required thyroid hormone therapy. Pharmacotherapy was initiated within 1 year in 5 of these 10 patients (50%), and between 1 and 3 years in the remaining 5 patients. No patient who did not undergo thyroidectomy required hormone therapy. Early evaluation of thyroid function appears important when postoperative RT, including CCRT, is performed in combination with TPLE or TL. CONCLUSION: Our study suggested that postoperative CCRT or RT after TPLE or TL, especially hemithyroidectomy, carries a high risk for hypothyroidism.

Day surgery for vocal fold lesions using a double-bent 60-mm Cathelin needle.

Day surgery for vocal cord lesions overcomes the disadvantages of laryngomicrosurgery under general anesthesia. We present our experience with treatment of vocal fold lesions using a long double-bend Cathelin needle that can access all parts of the vocal cords. A 23G, 60-mm-long Cathelin needle was bent twice by 45(o) at a distance of 1 and 2 cm from the tip, and was attached to a syringe. Under topical anesthesia and nasal endoscopy of the laryngopharynx, the needle was inserted percutaneously perpendicular to the skin, the direction of insertion being altered when the bends in the needle reached the skin surface. This allows the tip of the needle to access all parts of the glottis, allowing the performance of procedures such as biopsies, excision of lesions, and injection into the vocal folds. Between January 2011 and December 2013, we used this technique to perform vocal fold procedures in 566 patients presenting for treatment of spasmodic dysphonia (412 cases, 73 %) and other vocal fold lesions. Only minor complications, such as hematoma (3 patients, 0.5 %) and slight bleeding from the puncture site in the epiglottic vallecula (all patients, 100 %), which ceased spontaneously within 10 min, were seen. Erroneous puncture occurred in three patients (0.5 %) and the puncture had to be repeated in 38 patients (6.7 %). The procedure was completed successfully in all cases (100 %). Surgery for vocal fold lesions under topical anesthesia using our double-bend Cathelin needle technique is simple, safe, and useful.

Fenestration Approach for Arytenoid Adduction in Unilateral Vocal Fold Paralysis.

OBJECTIVE: Several surgical techniques have been reported for the treatment of unilateral vocal fold paralysis (UVFP). Although the fenestration approach has recently been applied for arytenoid adduction (AA) in some cases, long-term large-cohort studies on its usefulness are lacking. Therefore, this study aimed to evaluate the long-term voice outcomes of this technique in patients with UVFP. STUDY DESIGN: Retrospective study. METHODS: A total of 168 patients with UVFP underwent laryngoplasty comprising AA performed through fenestration of the thyroid ala combined with a type I thyroplasty (TPI). The maximum phonation time (MPT) and mean airflow rate (MFR) were measured before and after surgery, and voice analysis included an estimation of shimmer and jitter. Anterior and posterior surgical windows were created in the lower thyroid ala and were used for typical TPI and AA, respectively. The window locations were determined based on three-dimensional computed tomography data. AA was performed by pulling the muscular process of the arytenoid cartilage toward the lateral cricoarytenoid muscle through the posterior window without releasing the cricothyroid joint. All surgeries were performed under local anesthesia, and medialization was endoscopically confirmed. RESULTS: Postoperative MPT >10 seconds was achieved in 156 of the 168 patients. Postoperatively, MFR improved to <250 mL/s in all but two patients, and MPT, MFR, jitter, and shimmer significantly improved in all patients. Furthermore, perceptual evaluation using the Grade, Roughness, Breathiness, Asthenia, and Strain scale revealed significant improvement in all patients. CONCLUSIONS: The fenestration approach preserves the cricothyroid joint and does not open the cricoarytenoid joint; therefore, the laryngeal cartilage is stabilized, and no distortion of the laryngeal framework occurs. Our results showed that combined AA and TPI via the fenestration approach provided stable long-term postoperative voice improvement in patients with UVFP. LEVEL OF EVIDENCE: Level 3.

A Case of Laryngeal Cryptococcosis that Responded to Itraconazole.

Laryngeal cryptococcosis is a rare condition. While there is no reliable evidence regarding the treatment of laryngeal cryptococcosis, oral fluconazole was successful in most previous cases. We experienced a case where we could not continue fluconazole because of adverse drug effects. An 88-year-old female was referred to our department with a 5-month history of sore throat and cough. She had used oral steroids and a corticosteroid inhaler for poorly controlled asthma. Flexible laryngoscopy showed leukoplakia of the vocal cords and subglottic mucosa, and biopsy revealed cryptococcal infection. We started the treatment with fluconazole but changed to itraconazole because of adverse events. Since laryngoscopy performed 6 months later was unremarkable and drug interactions had occurred, we stopped the itraconazole use at 6 months. Our experience suggests that itraconazole is also useful for treating laryngeal cryptococcosis.

Detection of passive movement of the arytenoid cartilage in unilateral vocal-fold paralysis by laryngoscopic observation: useful diagnostic findings.

In a previous study of patients with unilateral vocal-fold paralysis (UVFP), three-dimensional computed tomography (3DCT) revealed passive movement during phonation, with the arytenoid cartilage on the paralyzed side pushed to the unaffected side and deviated upwards. The present work compares the 3DCT findings with those obtained by 2-dimensional endoscopy to visualize the vertical passive movement of the arytenoid cartilage. The study population consisted of 23 patients with UVFP and two with laryngeal deviation but normal movement of the vocal folds. Two endoscopic findings represented cranial deviation during phonation: posterior deviation of the arytenoid hump and lateral deviation of the muscular process. These two findings were classified into four grades, ranging from 0 (normal) to 3 (severe). Cranial displacement detected by 3DCT was also classified into four grades. Significant correlations were found between the 3DCT-determined grade of cranial displacement of the arytenoid cartilage and the grade assigned based on the two endoscopic findings. Moreover, lateral deviation of the muscular process was more significantly correlated with 3DCT grade than with endoscopic grade. Thus, endoscopic findings may be useful in the diagnosis of vocal-fold paralysis, and passive lateral deviation of the muscular process as an indicator of UVFP.

Effectiveness of Breath-holding Pulling Exercise in Patients with Vocal Fold Atrophy.

OBJECTIVE: In recent years, the incidence of vocal fold atrophy has increased among the elderly. Vocal function exercises (VFE) are performed in patients with age-related vocal fold atrophy; however, treatment could be challenging if the patient is unable to go to the hospital or in hospitals that do not have a speech pathologist. Breath-holding pulling exercises are simple and can be performed anywhere for the management of such patients. This study aimed to examine the effectiveness of breath-holding pulling exercises in patients with vocal fold atrophy. STUDY DESIGN: Retrospective study METHODS: With the hands folded in front of the chest, the patients were instructed to take a deep breath, pull their hands to the left and right, and then hold their breath for 5 seconds. The physician instructed the patients to do this 10 times each morning, afternoon, and evening. Speech function, acoustic analysis, pitch range, and Voice Handicap Index-10 (VHI-10) were evaluated and compared before and 4-8 weeks after treatment. RESULTS: Maximum phonation time (MPT), the primary endpoint, significantly improved after treatment from 14.2 ± 6.6 to 20.3 ± 9.3 seconds. Among the secondary endpoints, mean flow rate (207.5 ± 104.4 to 165.1 ± 66.5 mL/s), pitch range (22.9 ± 8.3 to 26.2 ± 8.1 semitones), VHI-10 (18.1 ± 7.2 to 12.5 ± 6.3 points) jitter (2.5±1.6 to 1.7±1.2%), and shimmer (5.9±3.5 to 4.8±3.3%) showed significant improvement. CONCLUSION: Breath-holding pulling exercises were found to be effective in patients with vocal fold atrophy. These can be performed in hospitals with no speech pathologists, in patients who are unable to go to the hospital, and in patients who are hospitalized or unable to speak loudly. Moreover, as with conventional VFE, the training method achieves a high level of patient satisfaction.

Over-injection of autologous fat in the vocal fold: how to remove the excess?

Chordal injection of autologous fat is useful in treating incomplete closure of the glottis on phonation, because it is simple, uses an intraoral approach and is mostly effective. However, when excess fat is injected, the removal of the excess is generally much more difficult than the injection. A 48-year-old man underwent intrachordal injections of autologous fat twice bilaterally for vocal fold atrophy. He came to our hospital because his hoarseness became worse after every operation. Three-dimensional computed tomography revealed that a large amount of fat was injected in the bilateral subglottal and glottic regions. These findings indicated that his dysphonia was due mainly to the excessive injected fat, and removal of the fat was planned. Under local anesthesia, we partially removed the excess fat through a window made in the thyroid cartilage, without touching the vocal folds. The voice and laryngeal findings were monitored during the surgery according to fiber-stroboscopic findings. Postoperatively, a significant improvement was seen in the voice and vibration of the vocal folds, although the results were not completely satisfactory.

Prevention of anastomotic leak using an advanced pectoral flap in total pharyngolaryngectomy and free jejunal reconstruction for hypopharyngeal or laryngeal carcinoma.

BACKGROUND: We devised an advanced pectoral flap (APF) to prevent anastomotic leak after total pharyngolaryngectomy (TPL) and free jejunal reconstruction (FJR) in patients with hypopharyngeal or laryngeal carcinoma. The APF alleviates tension on the skin in the neck, reduces the subcutaneous dead space, and promotes adhesion between the neck skin and the anastomosis. OBJECTIVE: To investigate whether an APF is effective for prevention of anastomotic leak associated with TPL/FJR. PATIENTS AND METHODS: Anastomotic leak was compared between APF (n = 65) and non-APF groups (n = 25). Patients who had received preoperative radiotherapy or undergone tracheostomy or skin infiltration requiring neck reconstruction using a pedicle flap were excluded. RESULTS: There were significantly fewer cases of anastomotic leak in the APF group than in the non-APF group (1.5% [1/65] vs. 16.0% [4/25]; p = .02). An APF could be created bilaterally within approximately 15 minutes. Unlike a deltopectoral flap, an APF does not require a skin graft. CONCLUSIONS: The postoperative anastomotic leak rate was 1.5% in patients who underwent TPL and FJR for hypopharyngeal or laryngeal carcinoma with an APF. SIGNIFICANCE: An APF is easily created and can reduce the incidence of anastomotic leak after TPL and FJR.

Mild pulmonary emphysema a risk factor for interstitial lung disease when using cetuximab for squamous cell carcinoma of the head and neck.

BACKGROUND: Interstitial lung disease (ILD) is an occasionally fatal adverse event associated with cetuximab (Cmab) therapy. Our objective was to clarify to what degree pulmonary emphysema is a risk factor in the treatment of head and neck cancer with Cmab through a retrospective analysis. METHODS: Subjects were 116 patients who were administered Cmab for head and neck squamous cell carcinoma. The degree of pulmonary emphysema before initiating treatment with Cmab was visually assessed retrospectively, with scoring according to the Goddard classification used in Japanese chronic obstructive pulmonary disease (COPD) guidelines for chest computed tomography (CT). Scoring was conducted by two diagnostic radiologists and mean scores were used. Cutoffs for the development and nondevelopment of ILD were examined by receiver operating characteristic (ROC) analysis and Fisher's exact test. Values of p < .05 were considered to indicate a significant difference. RESULTS: Among the 116 patients, 11 (9.5%) developed ILD, and 105 (90.5%) did not. In ROC analysis, the optimal Goddard score cut-off of <3.0 offered 55% sensitivity and 81% specificity (p = .015). With a cutoff of <3.0, even very mild pulmonary emphysema would represent a risk factor for ILD when using Cmab.

Thyroid Carcinoma on the Side of the Absent Lobe in a Patient with Thyroid Hemiagenesis.

BACKGROUND: Thyroid carcinoma complicated by hemiagenesis is very rare, and previous reports have not described this cancer on the side of the absent lobe. METHODS AND RESULTS: We report the case of a 64-year-old woman in whom left thyroid hemiagenesis was discovered incidentally during investigations of abnormal sensation during swallowing. A tumorous 1.4 cm lesion was also found on the side of the absent lobe, left of the isthmus. Fine-needle aspiration biopsy revealed class V papillary carcinoma, but no lymph node metastases. Total thyroidectomy was performed for stage cT1bN0M0 carcinoma. Histopathology revealed normal thyroid tissues in the right lobe and isthmus, while the left lobe was absent. The mostly papillary carcinoma was adjacent to the truncated thyroid tissue, with a portion histologically consistent with poorly differentiated carcinoma. CONCLUSIONS: All previously reported cases of thyroid cancer complicated by hemiagenesis have represented carcinoma occurring within the present lobe. This case is extremely rare.

Deep neck cellulitis: limitations of conservative treatment with antibiotics.

CONCLUSION: When the parapharyngeal space is infected, concurrent involvement of other spaces is likely, and involvement of multiple deep neck spaces is a key risk factor for abscess formation. OBJECTIVES: Deep neck infection is treated with antibiotics when abscesses have not yet been formed. However, in some cases, abscesses will form later and surgical drainage is warranted. This study retrospectively examined which cases were less likely to achieve cure, to clarify the limitations of conservative treatment for deep neck cellulitis. PATIENTS AND METHODS: Subjects comprised 19 patients with deep neck cellulitis who initially underwent conservative treatment with antibiotics. Patients were divided into two groups: Group A (n = 7), patients who recovered by conservative treatment; and Group B (n = 12), patients who did not recover and underwent surgical drainage. Age, state of DM control, etiology, treatment, spaces infected, and duration of hospitalization were investigated. RESULTS: The number of infected spaces was one in all Group A patients, whereas Group B showed multiple infected spaces in all except two cases. In particular, among the 10 cases with parapharyngeal space infection, eight (80%) showed multiple lesions.

The efficiency and adverse events of radiotherapy with cetuximab for Japanese head and neck cancer patients.

OBJECTIVES: Radiotherapy with cisplatin (Chemoradiotherapy, CRT) has long been one of the standard treatments for head and neck squamous cell cancer (HNSCC). Approval of cetuximab for the treatment of HNSCC has made radiotherapy with cetuximab (Bioradiotherapy, BRT) a new treatment option for HNSCC. Reports of BRT in the Japanese written in English up to now is only the phase II study, though it includes only 22 patients. Also on the nature of the clinical Phase II trial, sampling bias of cases may exist. Here we report the treatment completion rate, response rate and frequency of adverse events of BRT in Japanese patients with HNSCC in English for the first time. In association with this, we examine the issues related to BRT in Japanese patients. PATIENTS AND METHODS: The subjects consisted of patients with HNSCC who underwent BRT as the first curative treatment (45 cases). Their treatment completion rate, response rate and frequency of adverse events were examined. RESULTS: Of the 45patients, 42 were male and 3 were female. The mean age of the patients was 64 (range from 40 to 86). Adverse events of Grade3 or more were 12 cases (27%) of dermatitis, 31 cases (69%) of mucositis/stomatitis, 6 cases (13%) of interstitial pneumonia. The complication rate of pulmonary emphysema in those who developed interstitial pneumonia and those who did not were 83% and 21%, respectively. The BRT completion rate was 78%, and the response rate was 84%. CONCLUSION: BRT is sufficiently tolerable and have high response rate even for the Japanese, but we should recognize that BRT is not a minimally invasive and easily manageable treatment.

Features of Vocal Fold Adductor Paralysis and the Management of Posterior Muscle in Thyroplasty.

OBJECTIVE: To present the pathologic characteristics of unilateral recurrent nerve adductor branch paralysis (AdBP), and to investigate the management of posterior cricoarytenoid (PCA) muscle on the basis of our experience of surgical treatment for AdBP. STUDY DESIGN: This is a retrospective review of clinical records METHODS: Four cases of AdBP, in which surgical treatment was performed, are presented. AdBP shows disorders of vocal fold adduction because of paralysis of the thyroarytenoid and lateral cricoarytenoid muscles. The PCA muscle, dominated by the recurrent nerve PCA muscle branch, does not show paralysis. Thus, this type of partial recurrent nerve paresis retains the abductive function and is difficult to distinguish from arytenoid cartilage dislocation because of their similar endoscopic findings. The features include acute onset, and all cases were idiopathic etiology. Thyroarytenoid muscle paralysis was determined by electromyography and stroboscopic findings. The adduction and abduction of paralytic arytenoids were evaluated from 3 dimensional computed tomography (3DCT). RESULTS: In all cases, surgical treatments were arytenoid adduction combined with thyroplasty. When we adducted the arytenoid cartilage during inspiration, strong resistance was observed. In the two cases where we could cut the PCA muscle sufficiently, the maximum phonation time was improved to ≥30 seconds after surgery, from 2 to 3 seconds preoperatively, providing good postoperative voices. In contrast, in the two cases of insufficient resection, the surgical outcomes were poorer. CONCLUSIONS: Because the preoperative voice in AdBP patients is typically very coarse, surgical treatment is needed, as well as ordinary recurrent nerve paralysis. In our experience, adequate PCA muscle resection might be helpful in surgical treatment of AdBP.

A case of giant osteoma in the middle turbinate of a child.

Only seven cases of osteoma arising in the middle turbinate have been reported to date. We report the eighth case, involving osteoma in the middle turbinate of a child. This young boy was initially examined at the age of nine for the main complaint of nasal obstruction. Although a large osteoma with a maximum diameter of 30 mm was observed on computed tomography (CT), the patient was only observed because of the wishes of the family. At 13 years, he was again examined, as a result of worsening of the nasal obstruction. CT revealed that the osteoma had enlarged to a maximum diameter of 41 mm. Endoscopic surgery was attempted, but because of difficulties, the osteoma instead had to be removed under direct vision via a gingival incision. The final pathological diagnosis was osteoid osteoma. The nasal obstruction disappeared following surgery, with no recurrence after more than 12 months postoperatively.

Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas.

CONCLUSION: Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma. OBJECTIVE: A patient diary was constructed to determine the effectiveness of concomitant antiemetic therapy with a neurokinin-1 receptor antagonist (fosaprepitant), 5-hydroxytryptamine receptor antagonist (palonosetron), and dexamethasone in accordance with guidelines. METHODS: Subjects comprised 41 patients who received 71 courses of chemotherapy, along with fosaprepitant, palonosetron, and dexamethasone. A patient diary was compiled concerning the presence/absence of vomiting, vomiting episodes, presence/absence of rescue therapy, food intake, presence/absence of nausea, and general condition. RESULTS: The frequency of the primary end point of complete response in the overall phase was 69.0%. The proportion of patients with no vomiting in the overall phase was 90.1%. In the acute phase, the proportion of no nausea and slight nausea together was 91.5%, no change in and slightly reduced food intake together was 87.3%, and the proportion of good general condition and relatively good general condition was 85.9%. In the delayed phase, the proportion of no nausea and slight nausea together was 56.3%, no change in and slightly reduced food intake together was 43.7%, and the proportion of good general condition and relatively good general condition together was 53.5%.

Prospective Randomized Trial on Postoperative Administration of Diet Containing Eicosapentaenoic Acid, Docosahexaenoic Acid, Gamma-linolenic Acid, and Antioxidants in Head and Neck Cancer Surgery Patients with Free-flap Reconstruction.

OBJECTIVES: The purpose of this prospective, randomized study was to evaluate the effects of a diet containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), and antioxidants in head and neck cancer surgery patients with free-flap reconstruction. METHODS: In this randomized, prospective study, 62 patients with head and neck cancers were assigned to receive a general control diet (Ensure(®) H; Abbott Japan, Tokyo, Japan) or the study diet (Oxepa(®); Abbott Japan) containing EPA, DHA, GLA, and antioxidants (eg vitamins A, E, and C). The primary assessment item was the degree of postoperative inflammation, as assessed by measuring maximum body temperature and levels of C-reactive protein (CRP) and procalcitonin from the day of surgery to postoperative day 8. Secondary assessment items were lengths of stays in the intensive care unit (ICU) and hospital. RESULTS: The control diet group (n = 32) and study diet group (n = 30) showed no significant difference in energy administered through diet. No significant differences in the parameters of the primary assessment item were noted. Length of stay in the ICU was significantly shorter for the control diet group than for the study diet group (P = 0.011). No significant difference in duration of hospitalization was seen between groups. CONCLUSION: No usefulness of a diet containing EPA, DHA, GLA, and antioxidants was demonstrated.

Joint use of skull base surgery in a case of pediatric parotid gland carcinoma.

Parotid gland carcinoma is extremely rare in children. We report a case of pediatric parotid gland carcinoma with extensive infiltration into surrounding tissues including the skin and temporomandibular joint capsule at initial examination. Total resection of the parotid gland was conducted together with skull base surgery and mandibular dissection. The patient was a 14-year-old girl. In addition to the skin and temporomandibular joint, infiltration into the anterior wall of the external auditory meatus and masseter muscle was also seen, and T4N0M0 stage IV parotid carcinoma was diagnosed. Skin was resected together with the pinna, and temporal craniotomy and skull base surgery were performed to resect the temporomandibular joint capsule and external auditory meatus en bloc, and mandible dissection was conducted. Facial nerves were resected at the same time. Level I to level IV neck dissection was also conducted. A latissimus dorsi myocutaneous flap was used for reconstruction. The postoperative permanent pathology diagnosis was high-grade mucoepidermoid carcinoma with a low-grade component. Postoperatively, radiotherapy at 50 Gy alone has been conducted, with no recurrence or metastasis observed for over 4 years.

A case report of malignant melanoma of the sphenoid sinus.

Malignant melanoma of the sphenoid sinus is a very rare disease, and only 6 cases have previously been reported. The present case involved a 74-year-old woman who was examined for visual disturbance of the left eye. Computed tomography revealed a soft tissue shadow, but only mucosal hypertrophy was found on opening the sphenoid sinus under general anesthesia. One month postoperatively, visual disturbance of the right eye and paresis of cranial nerve III appeared. Malignant melanoma was diagnosed from biopsy. Multiple bone metastases were identified, but the patient declined active treatment. As a result, palliative care was provided and she died 3 months later. When there is no improvement in postoperative visual acuity as in this case, in consideration of the possibility of neoplastic lesions, rigorous followup including monitoring for neurological symptoms is warranted.

A case of primary submandibular gland oncocytic carcinoma.

Primary submandibular gland oncocytic carcinoma is a rare pathology, with only 10 cases being reported to date. We encountered a case of primary submandibular gland oncocytic carcinoma and report it herein. The patient was a 69-year-old man who came to our hospital with right submandibular cancer as the main complaint. Based on the results of computed tomography and magnetic resonance imaging, submandibular gland tumor was diagnosed. Preoperative cytodiagnosis suggested class III oncocytic carcinoma. Resection of the right submandibular tumor was performed along with right neck dissection. Postoperative histopathological diagnosis was oncocytic carcinoma. As of 3 years following surgery, no recurrence has been identified.

Two Cases of Small Cell Cancer of the Maxillary Sinus Treated with Cisplatin plus Irinotecan and Radiotherapy.

Background. Small cell carcinoma (SmCC) in the nasal cavity and paranasal sinuses is very rare, and definitive therapies have not yet been established. Methods. Chemoradiotherapy comprised 60 Gy of external radiation, with the administration of irinotecan intravenously at 60 mg/m(2) on days 1, 8, and 15 and cisplatin at 60 mg/m(2) on day 1. Results. Case 1 involved a 66-year-old woman with stage III cancer. Adverse events included decreased white blood cells, anemia, and oral mucositis, all Grade 2. The patient remained free of cancer as of 3 years and 6 months after completing the treatment. Case 2 involved a 60-year-old man with stage IV cancer. He also experienced adverse events of decreased white blood cells, anemia, and oral mucositis, all Grade 2. He died after 11 months due to metastases throughout the body. Conclusions. The results suggest that this regimen may be tolerable as a therapy for this type of carcinoma.