Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-year results of the Phase 3 Mammella InterGruppo (MIG)-1 study.

BACKGROUND: Adjuvant chemotherapy is the standard of care in high-risk early breast cancer patients. Dose-dense should be the preferred schedule of administration. However, its long-term benefit is unknown. METHODS: In the Italian multicentre Phase 3 randomised MIG-1 trial, node-positive and high-risk node- negative breast cancer patients were randomised to receive six cycles of adjuvant fluorouracil, epirubicin and cyclophosphamide regimen administered every 3 (FEC21) or 2 (FEC14) weeks. The primary endpoint was overall survival (OS), and the secondary endpoint was event-free survival (EFS). RESULTS: From 1992 to 1997, 1214 patients were included. Median follow-up was 15.8 years. In all, 15-year OS was 71% and 68% in the FEC14 and FEC21 groups, respectively (HR = 0.89; p = 0.25). In all, 15-year EFS was 47% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.87; p = 0.18). In a pre-planned subgroup analysis, among patients with hormone receptor-negative tumours, 15-year OS was 70% and 65% in the FEC14 and FEC21 groups, respectively (HR = 0.73; 95% CI: 0.51-1.06); 15-year EFS was 58% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.70; 95% CI: 0.51-0.96). CONCLUSIONS: Updated results from the MIG-1 study are numerically in favour of dose-dense chemotherapy, and suggest a long-term benefit of this approach in high-risk early breast cancer patients.

Phase III Randomized Study of Induction Chemotherapy Followed by Definitive Radiotherapy + Cetuximab Versus Chemoradiotherapy in Squamous Cell Carcinoma of Head and Neck: The INTERCEPTOR-GONO Study (NCT00999700).

OBJECTIVES: Induction chemotherapy followed by cetuximab and RT (IBRT) (Arm A) was compared to cisplatin/RT (CRT) (Arm B) in a randomized phase III study. PATIENTS AND METHODS: Naïve patients with stage III-IVa, histologically proven locally advanced head and neck cancer (LASCCHN) were eligible. Arm A (IBRT): 3 TPF induction followed by cetuximab-RT (equivalent daily dose 2 Gy up to 70 Gy); Arm B: 3 cisplatin concurrent with the same RT scheduling. Due to slow accrual and incomplete data collection a futility analysis was performed. RESULTS: 236/282 patients were evaluable. Therefore, no formal analyses can be made between the two arms. OS was 45.2/53.6 months in Arm A/B. Complete responses were achieved in 64% of patients in both arms. Neutropenia and skin toxicity were significantly worse in Arm A and body weight loss was significantly worse in Arm B. Compliance with the planned drug administration was higher in Arm B (p = 0.0008). CONCLUSION: The study suggests that IBRT and CRT have similar efficacy, activity and toxicity.

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis.

BACKGROUND: Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (2',2'-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. METHODS: We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3-4 acute mucositis rate. RESULTS: A total of 13 papers were eligible for the literature review. For schedules using a gemcitabine dose intensity (DI) below 50 mg/m(2) per week, the complete response rate was 86% (95% CI, 74%-93%) with grade 3-4 acute mucositis rate of 38% (95% CI, 27%-50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Compared with DI ≥50 mg/m(2) per week, there was no difference in the complete response rate (71%; 95% CI, 55%-83%; p = .087) but a significantly higher (p < .001) grade 3-4 acute mucositis rate of 74% (95% CI, 62%-83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%-63%). Late toxicity comprising mainly dysphagia was generally underreported, whereas information about xerostomia and skin fibrosis was scarce. CONCLUSION: This review highlights the radiosensitizing potential of gemcitabine and suggests that even very low dosages (less than 50 mg/m(2) per week) provide a sufficient therapeutic ratio and therefore should be further investigated. Refinements in radiation schemes, including intensity-modulated radiation therapy, in combination with low-dose gemcitabine and targeted agents, such as cetuximab, are currently being investigated. IMPLICATIONS FOR PRACTICE: Cisplatin-based concurrent chemoradiation (CCRT) has become the standard treatment of locally advanced head and neck cancer (LAHNC). This approach is hampered by significant toxicity. This paper reviews the studies using gemcitabine as an alternative radio-sensitizer for CCRT in patients with LAHNC. In this capacity, despite its mild intrinsic toxicity, gemcitabine comes with high rates of severe mucositis when used in dosages exceeding 50 mg/m(2) per week. CCRT with low-dose gemcitabine provides a sufficient therapeutic ratio, combining clinical activity, similar to the higher-dose regimens, with lower toxicity. Further investigation is warranted.

Muscle quality and not quantity as a predictor of survival in head and neck squamous cell carcinoma.

BACKGROUND: Sarcopenia is frequent in head and neck squamous cell carcinoma (HNSCC), as a consequence of malnutrition related to risk factors or tumoral mass. Treatment is associated with toxicities that lead to reduced calories intake and muscle mass wasting. Sarcopenia has been negatively associated with tumor control and survival outcomes. PURPOSE: Our aim is to evaluate the prognostic impact of sarcopenia on overall survival (OS) and progression free survival (PFS) in HNSCC patients undergoing chemoradiation therapy within a prospective clinical trial of chemoradiation vs induction chemotherapy followed by radiation and cetuximab (INTERCEPTOR). MATERIALS AND METHODS: On baseline CT or MRI, we investigated the association between OS and PFS with radiological markers of sarcopenia, measured at the third cervical vertebra level. We studied paravertebral skeletal muscles area (cm2), muscle density (HU), muscle index (cm2/m2), and intermuscular adipose tissue (IMAT) area (cm2). RESULTS: Imaging of 128 patients was evaluable. We found out that higher body mass index (BMI) was associated with better OS (p = 0.02), and PFS (p = 0.04). Skeletal muscle area (p = 0.02), and IMAT (p = 0.02) were negatively associated with PFS. IMAT was positively correlated with muscle area (Correlation coefficient 0.6, CI95% 0.47-0.7), and negatively associated with muscle density (Correlation coefficient -0.37, CI95% -0.53 - -0.18). CONCLUSIONS: IMAT can be used as predictor of PFS in HNC patients undergoing chemoradiation therapy. The amount of intermuscular fat deposits induces alterations of muscle quality, without alterations of muscle quantity, influencing patients' prognosis.

The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy.

PURPOSE: To date, the specific role of "in-field" crusting exudation on pain and on activity of daily living (ADL) in head and neck cancer (HNSCC) patients undergoing treatment with cetuximab and radiochemotherapy has been neglected. The purpose of the study was to evaluate the role of crusting exudation on the severity of pain and ADL METHODS: Thirty-seven of the 45 HNSCC patients enrolled in the alternating radiotherapy, chemotherapy, and cetuximab trial were evaluated in this study. The main radiodermatitis signs (the intensity of erythema, the extension of dry, and moist desquamation and of necrosis)--including crusting exudation severity--pain, ADL, and radiodermatitis scores were registered at least weekly during and after treatment. The correlation between crusting exudation and pain or ADL was evaluated. RESULTS: The "in-field" crusting exudation score seemed to have the strongest correlation with pain (Spearman's rho = 0.897; p < 0.001) and the most intense influence on it (Co-B = 0.715; 95% C.I. = 0.643-0.787). However, it seemed to have a weaker correlation with ADL than the other clinical radiodermatitis signs. CONCLUSIONS: Crusts have the strongest correlation with pain in patients with Cetuximab-related radiation dermatitis. Moreover, the presence of crusts can lead operators to misclassify dermatitis as score 4, causing unnecessary delays or interruptions in treatment.

Platinum-based chemotherapy plus cetuximab in head and neck cancer.

BACKGROUND: Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. METHODS: We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. RESULTS: Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P=0.04). The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group (P=0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. There were no cetuximab-related deaths. CONCLUSIONS: As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)

Selection of systemic therapy in patients with locally advanced and recurrent/metastatic head and neck cancer: RAND-based expert opinion by an Italian multidisciplinary panel.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease often presenting at an already advanced stage. Cisplatin chemoradiotherapy is the standard treatment for locally advanced disease, although its efficacy varies according to different studies. Thus, treatment selection is a challenge, especially in older patients, who frequently have several comorbidities. Moreover, the majority of patients with recurrent and/or metastatic disease are unsuitable for local treatment, either surgery or radiation therapy. The only treatment option for them is systemic therapy, but prognosis remains poor, with a median overall survival of less than 12 months. METHODS: A group of Italian key opinion leaders in the field of HNSCC gathered several times in 2018 in order to retrieve a set of statements to help clinicians in their daily decision-making process for the treatment of patients with different scenarios of HNSCC. RESULTS AND CONCLUSION: The panel agreed on 22 statements that were identified as "good clinical points" based on the available literature or after discussion of the most relevant aspect of the underlying diseases when no international consensus was available. The panel identified a number of possible scenarios (namely 71) in which these statements may be helpful to guide decision-making for the best treatment selection.

A phase II trial of low-dose gemcitabine and radiation alternated to cisplatin and 5-fluorouracil: an active and manageable regimen for stage IV squamous cell carcinoma of the head and neck.

BACKGROUND: The addition of gemcitabine may be a reasonable way to enhance the activity of the alternating cisplatin/5-fluorouracil and radiation regimen considered the referring approach for patients with advanced squamous cell carcinoma (SCC) of the head and neck at the National Institute for Cancer Research of Genoa. METHODS: Three courses of cisplatin, 20mg/m(2)/day and 5-fluorouracil, 200mg/m(2)/day, days 1-5 (weeks 1, 4, and 7) alternated to 3 courses of radiotherapy at standard fractionation (weeks 2-3, 5-6, 8-9) up to 60Gy, and gemcitabine, 50mg/m(2) on monday of each week of radiation, were administered to 47 patients with stage IV (42 patients) or relapsed after surgery (5 patients), SCC of the oral cavity, pharynx or larynx. RESULTS: Eighty-five percent of the patients completed the planned treatment. Main grade 3-4 acute toxicities were: mucositis (40%), neutropenia (26%) and thrombocytopenia (30%). Twenty-seven patients reached a complete response (57%). Seven partial responders were rendered disease-free by surgery (final complete response rate: 72%). At a median follow-up of 37 months, 3-year overall survival, progression-free survival and loco-regional control are 50%, 43% and 54%, respectively. CONCLUSIONS: The addition of gemcitabine at low dose to our referring alternating regimen is feasible and very active. It may improve the long-term outcomes despite an acceptable increase of acute mucoseal toxicity.

Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results.

Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.

Impact of treatment expertise on the outcome of patients with head and neck cancer treated within 6 randomized trials.

BACKGROUND: We evaluated the impact of center expertise, in terms of number of patients treated, on the overall survival (OS) and progression-free survival (PFS) of patients with head and neck squamous cell carcinoma (SCC). METHODS: We performed a pooled analysis including data from 6 randomized trials in head and neck SCC conducted in Italy. We evaluated the association between OS or PFS and the number of patients recruited by the center. RESULTS: The outcome of 903 patients who had received radiotherapy (RT) was analyzed (median follow-up 76 months). The hazard ratio (HR) comparing the third and the first quartiles of the distribution of number of patients per center showed an advantage in PFS (HR 0.59, range 0.53-0.65, P < .0001) and in OS (HR 0.70, 0.60-0.81, P < .0001) for centers with a higher number of patients recruited. A similar benefit was observed in PFS (HR 0.63, 0.60-0.66) and OS (HR 0.74, 0.69-0.79) considering the mean number of patients per year. CONCLUSIONS: The PFS and OS were longer for patients treated in high-case-volume centers.

Two-stage hepatectomy in two regional district community hospitals: perioperative safety and long-term survival.

INTRODUCTION: Surgical resection offers the best chance of cure for patients with colorectal liver metastases (CRLMs). Two-stage hepatectomy (TSH) has been demonstrated to be safe and effective to obtain curative resection in patients with multiple, bilobar CRLMs that are unresectable in a single procedure. Up to now TSH has been the prerogative of dedicated liver surgery centers. The aim of this study was to assess the safety and effectiveness of TSH also in community hospitals. METHODS: Of 294 patients operated on for CRLMs between September 1997 and June 2012 in 2 district community hospitals (belonging to the same regional healthcare district), 43 (14.6%) were scheduled for TSH. Thirty-eight/43 received neoadjuvant and/or bridge chemotherapy (2 neoadjuvant only, 4 neoadjuvant and bridge, 32 bridge only). RESULTS: The mean follow-up was 35.74 ± 29.53 months. Five-year overall survival (OS) was 31.4%, with a median survival time of 31 months. Twenty-nine patients completed the planned procedure (OS: 42.9%; median 47 months), while 14 did not because of disease progression (OS: 0%; median 13 months). No operative mortality occurred within the first 90 days either after the first or second stage. CONCLUSIONS: Our results suggest good efficacy and safety of TSH even when performed in a community hospital setting. Shifting patient selection from neoadjuvant to bridge chemotherapy had no impact on outcome once the clearing of the liver had been achieved. In patients presenting with synchronous CRLMs, simultaneous colorectal resection and clearing of the less involved hemiliver as the first surgical step is feasible without any negative impact on outcome.

Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies.

BACKGROUND: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea. PATIENTS AND METHODS: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates. RESULTS: A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54-0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54-1.12) and 0.65 (95% CI, 0.40-1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80-1.25; p = 0.989). CONCLUSION: Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.

Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus.

The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics.

Contralateral parotid-sparing radiotherapy in patients with unilateral squamous cell carcinoma of the head and neck: technical methodology and preliminary results.

AIMS AND BACKGROUND: Radiation-induced permanent xerostomia occurs frequently in patients affected by squamous cell carcinoma of the head and neck treated by parallel opposed lateral fields. An ipsilateral technique by using co-planar multiple-field arrangement was designed to restrict treatment to the primary tumor and neck on the same side for patients with selected lateralized squamous cell carcinoma of the head and neck. METHODS: From November 2001 till December 2002, 30 patients affected by squamous cell carcinoma of tonsillar fossa, retromolar trigone, alveolar ridge and oropharyngeal lateral wall were included in this investigational trial and treated with an ipsilateral multiple field technique: in detail, oblique opposed two upper half fields were planned ipsilaterally to the squamous cell carcinoma site to cover PTV1 and PTV2, whereas an anterior-lower half field was planned to encompass the lower neck node area above clavicles. On CT scans, the contralateral parotid gland was outlined as organ at risk and the contralateral upper lymph node area was contoured as volume of interest. In selected cases, convergent oblique two wedge-pair half fields were added to opposed oblique two-field technique in order to cover only PTV2: generally, in these patients, PTV1 received 1.8 Gy per fraction and PTV2 2.2 Gy per fraction up to total doses of 54 Gy and 66 Gy, respectively. RESULTS: Ten patients received radical radiotherapy, 9 patients radical alternating chemo-radiotherapy, and 11 patients adjuvant radiotherapy. At the end of treatment, unilateral confluent mucositis was recorded in 13 (43%) patients and unilateral moist skin epidermolysis in 14 (46%) patients. Six months after the end of radiotherapy, grade 0 xerostomia was recorded in 20 (67%) patients. No patient experienced grade 2+ xerostomia. At a median follow-up of 12 months, 26 (86%) patients were alive and well; 2 patients (6%) developed contralateral neck node failure, both 4 months after the end of ipsilateral radiotherapy. CONCLUSIONS: These results, although preliminary, suggest that by using an ipsilateral radiotherapy technique, symptomatic xerostomia may be avoided in selected patients with lateralized squamous cell carcinoma of the head and neck without an increased short-term risk of contralateral nodal failure.

Late local treatment morbidity after accelerated radiotherapy or alternating chemoradiotherapy for advanced head and neck carcinoma.

BACKGROUND: To report local long-term morbidity after concomitant boost radiotherapy (AFRT) or alternating chemoradiotherapy (CTRT), we analyzed the toxicity data recorded in 168 patients with advanced head and neck squamous cell carcinoma treated at our institution within phase II-III studies. PATIENTS AND METHODS: All patients enrolled in three consecutive phase II-III studies and followed for a minimum of three months after the end of treatment were included in the present analysis. Local late reactions were scored prospectively. The actuarial incidence of grade 2 or more (2-4) late local toxicity according to RTOG/EORTC was taken as endpoint. The median follow-up is 32.0 months (range, 3.3-138.1 months). For living patients the minimum and median follow-up are 12.1 and 69.3 months, respectively. RESULTS: The five-year actuarial incidence of grade 2+ and grade 3+ toxicity are 56.7 +/- 5% and 21 +/- 4%, respectively. At multivariate analysis, acute mucositis grade, complementary surgery, primary site and performance status proved to be independent predictive factors of grade 2+ late toxicity with P values of <0.001, 0.009, 0.022 and 0.033, respectively. No effect was found for treatment itself on the incidence of late toxicity, although patients treated with accelerated radiotherapy had a higher probability of confluent mucositis than patients treated with alternating chemoradiotherapy (68% vs 32%, P <0.01). CONCLUSIONS: A substantial proportion of surviving patients develops late complications, although severe irreversible reactions occur in a minority of patients. Acute local toxicity can be used to predict local late toxicity that arises within five years of the end of treatment.

Induction chemotherapy for squamous cell head and neck cancer: a neverending story?

Induction chemotherapy prior to planned definitive local therapy for head and neck squamous cell carcinoma has been studied for at least three decades but the debate on its role is still open. Recent landmark studies, including those presented at outstanding meetings and those still ongoing on induction chemotherapy in different clinical situations, are critically reviewed. Data confirm that a docetaxel, cisplatin and 5-fluorouracil (TPF) based induction chemotherapy may be considered in clinical practice as one of the possible options when a larynx preservation strategy is attempted. On the contrary, current data do not support the use of induction chemotherapy before a planned surgical intervention for advanced oral cavity and oropharyngeal tumors. Currently, for patients with locoregionally advanced unresectable disease, concomitant chemo-radiation remains the standard of care in waiting for results of the few ongoing studies that hopefully will clarify the role of induction TPF before either concomitant chemo-radiation or bio-radiation.

Paclitaxel, cisplatin and 5-fluorouracil in recurrent squamous cell carcinoma of the head and neck: a phase II trial from an Italian cooperative group.

The aim of this multicenter trial was to test the feasibility and the activity of a three-drug combination where paclitaxel is added to cisplatin and 5-fluorouracil. Patients with metastatic or relapsed SCC-HN unsuitable for further loco-regional radical treatment, not previously treated with chemotherapy, were eligible to receive paclitaxel 160 mg/m2 (3-hr infusion) day 1, CDDP 25 mg/m2/day and 5-FU 250 mg/m2/day bolus on days 1, 2, 3 every three weeks up to a maximum of five courses. Fourty-seven patients were enrolled by five Institutions in Italy. Main grade III-IV toxicities were: neutropenia (48%), thrombocytopenia (6%), anemia (4%), diarrhea (2%), mucositis (2%). Six patients had a complete response (13.3%) and eight a partial response (17.8%). Median progression free survival and overall survival are 4.1 and 7.9 months. One-year progression free survival and overall survival are 16% and 29%. This three-drug regimen has an excellent safety profile. The activity in the palliation of recurrent SCC-HN, however, does not appear to be improved in comparison with cisplatin and 5-fluorouracil or cisplatin and paclitaxel regimens. Recent studies indicate a more promising role of taxanes including triplets in the induction therapy of previously untreated patients.

Quimioterapia basada en platino más cetuximab en el cáncer de cabeza y cuello / Platinum plus cetubimab based quimiotherapy in head and neck cancer

Antecedentes: Cetuximab resulta efectivo en el carcinoma metastático o recurrente de células escamosas de cabeza y cuello, resistente al platino. Se investigó la eficacia de cetuximab más quimioterapia basada en platino como tratamiento de primera línea en pacientes con carcinoma metastático o recurrente de células escamosas de cabeza y cuello. Métodos: Se asignaron al azar 220 pacientes de 442 pacientes elegibles con carcinoma metastático o recurrente de células escamosas de cabeza y cuello sin tratamiento, para recibir cisplatino (a una dosis de 100mg por metro cuadrado de área de superficie corporal el día 1) o carboplatino (en un área por debajo de la curva de 5mg por mililitro por minuto, como infusión intravenosa de 1 hora el día 1) más fluorouracilo (a una dosis de 1000mg por metro cuadrado por día, durante 4 días) cada 3 semanas, por un máximo de 6 ciclos, y 222 pacientes para recibir la misma quimioterapia más cetuximab (a una dosis de 400mg por metro cuadrado en forma inicial, como infusión intravenosa de 2 horas, luego 250mg por metro cuadrado, como infusión intravenosa de 1 hora por semana) durante un máximo de 6 ciclos. Los pacientes con enfermedad estable que recibieron quimioterapia más cetuximab continuaron recibiendo cetuximab hasta la progresión de la enfermedad o hasta la aparición de efectos tóxicos inaceptables, lo que ocurriera primero. Resultados: El agregado de cetuximab a la quimioterapia basada en platino con fluorouracilo (platino-fluorouracilo) prolongó de manera significativa la mediana de la supervivencia global, de 7.4 meses en el grupo de quimioterapia sola a 10.1 meses en el grupo que recibía quimioterapia más cetuximab (índice de riesgo para muerte = 0.80; intervalo de confianza 95%: 0.64-0.99; p = 0.04). El agregado de cetuximab prolongó la mediana del tiempo de supervivencia libre de progresión de 3.3 meses a 5.6 meses (índice de riesgo para la progresión = 0.54; p < 0.001) y aumentó la tasa de respuesta de 20% a 36% (p < 0.001).