Adjuvant chemotherapy in stage II breast cancer: A brief overview of the NSABP clinical trials

Since 1972 the National Surgical Adjuvant Breast and Bowel Project (NSABP) has completed 5 adjuvant chemotherapy protocols into which over 3,500 histologically nodepositive patients have been entered; data for this review are derived predominantly from the first 3 studies. Each study was performed sequentially with the intent of identifying patient subsets responding to 1, 2, or 3 chemotherapeutic agents. Comparison of disease-free survival in patients receiving l-phenylalanine mustard (L-PAM) or placebo after 10 years of follow-up disclosed that L-PAM was beneficial in patients up to 49 years of age, but not in women 50 years. Further analysis indicated that the subset of patients 49 years with 1–3 positive nodes sustained the greatest increment in disease-free survival with single-agent L-PAM. The addition of 5-fluorouracil (5-FU) to L-PAM was superior to L-PAM alone in patients 50 years of age, particularly those with 4 positive nodes. This effect became attenuated after 6 years of follow-up. The 3-drug regimen of L-PAM, 5-FU, and methotrexate failed to provide a benefit over and above that achieved by the L-PAM-5-FU combination in all subsets examined. Two further NSABP protocols are described in which the addition of Adriamycin^® to L-PAM and 5-FU is addressed. The rationale for the current generation of NSABP adjuvant chemotherapy trials using short intensive Adriamycin^® and cyclophosphamide regimens is discussed. The results continue to underscore the heterogeneous response to chemotherapy demonstrated by patient subsets characterized on the basis of age and nodal status.

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Resumen A partir de 1972 el NSABP (National Surgical Adjuvant Breast and Bowel Project) ha completado cinco protocolos de quimioterapia adyuvante, al cual han ingresado 3,500 pacientes con ganglios histológicamente positivos; los datos que constituyen la presente revisión han sido derivados principalmente de los primeras tres estudios. Cada estudio fue realizado en forma secuencial con el objeto de identificar aquellos subgrupos de pacientes que respondían a 1, 2, o 3 de los agentes quimioterapéuticos. La comparación de los períodos o intervalos libres de enfermedad en pacientes que recibieron L-PAM o un placebo a los 10 años de seguimiento reveló que la L-PAM fue de beneficio en las pacients de 49 años de edad, pero nó en las de 50 años. Un análisis más profundo indicé que el subgrupo de pacientes de 49 años con 1–3 ganglios positivos exhibió el mayor incremento en el período libre de enfermedad con la L-PAM como único agente. La adición de 5-FU a la L-PAM apareció superior a la L-PAM sola en paciente de 50 años de edad, especialmente en aquellas con 4 ganglios positivos. Este efecto aparece atenuado después de 6 años de seguimiento. El regimen combinado con 3 drogas, L-PAM, 5-FU y metotrexato, no significó un beneficio mayor ni adicional que el logrado con la combinación L-PAM-5-FU en los subgrupos analizados. Se describen otros dos protocolos NSABP en los cuales se investiga la adición de Adriamicina a L-PAM y 5-FU. Se discute la razón por la cual actualmente se han generado dentro del NSABP, ensayos de quimioterapia a base de regimenes cortos de Adriamicina y ciclofosfamida. Los resultados continúan demostrando la heterogénea respuesta a la quimioterapia por parte de los diversos grupos de pacientes de acuerdo a la edad y al estado de sus ganglios.

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Résumé Depuis 1972 la formation NSABP (National Surgical Adjuvant Breast and Bowel Project) de Pittsburgh a appliqué à 3,500 malades dont les ganglions axillaires étaient histologiquement envahis 5 protocoles chimiothérapeutiques différents. Les données actuellement receuillies concernent essentiellement les 3 premiers protocoles. Chaque étude a été conduite séquentiellement avec l'intention d'identifier les sous-groupes de malades répondant respectivement à 1, 2, ou 3 agents médicamenteux. La comparaison de la survie sans récidive chez les malades recevant soit du L-PAM (l-phénylalanine mustard) soit un placebo après 10 ans d'évolution a permis de constater que le L-PAM exerçait une action bénéfique seulement chez les femmes âgées de moins de 50 ans. Une analyse plus poussée des malades appartenant à ce groupe a montré que l'action du L-PAM était plus efficace lorsque 1, 2, ou 3 ganglions seulement étaient envahis. L'adjonction de 5-fluorouracil (5-FU) au L-PAM a permis d'enregistrer une amélioration des résultats chez les malades âgés de plus de 50 ans, en particulier lorsque plus de 4 ganglions étaient envahis. L'effet bénéfique du traitement s'est atténué après 6 ans d'évolution. L'association L-PAM, 5-FU, méthotrexate n'a pas entraîné une amélioration des résultats thérapeutiques chez les malades appartenant aux différents sous-groupes traités. Deux nouveaux protocoles associant l'adriamycine au L-PAM ou au 5-FU ont été mis à l'étude. La raison d'employer d'autres nouveaux protocoles incluant l'adriamycine et la cyclophosphamide à haute dose pendant une courte période de temps est exposée. Les résultats ne font que souligner l'action variable de la chimiothérapie chez les malades qui appartiennent aux différents sous-ensembles définis en fonction de l'âge et de l'envahissement ganglionnaire.

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Supported by Public Health Service Grants from the National Cancer Institute (NCI-U10-CA-12027 and NCI-U10-CA-34211) and by a grant from the American Cancer Society (ACS-RC-13).     

Adjuvant chemotherapy in stage I and stage II testicular cancer

Adjuvant chemotherapy in low-stage testis cancer is an accepted treatment option for two clinical situations: (1) chemotherapy after complete removal of the primary tumor by orchidectomy without clinical evidence of metastasis (clinical stage I), and (2) chemotherapy after complete surgical removal of non-seminomatous retroperitoneal metastases up to 5 cm in greatest transverse diameter by retroperitoneal lymph node dissection in clinical stage II. Aim of treatment is the prevention of tumor recurrences. The risk of recurrence depends on the type and stage of disease and ranges from 16% (clinical stage I seminoma) to 50% (pathological stage II B non-seminoma). Thus, 50–84% of patients receive adjuvant treatment unnecessarily. Prognostic factors have been developed in each tumor entity to tailor treatment to patients with high risk of recurrence.     

Adjuvant radiotherapy and chemotherapy in breast cancer

Three hundred and twenty-two women with involvement of axillary lymph nodes following surgery for operable breast cancer were randomized to receive either postoperative radiotherapy, chemotherapy (CMF) or radiotherapy followed by chemotherapy. There was an increase in disease free interval in pre- and postmenopausal patients receiving radiotherapy and chemotherapy regardless of the number of nodes involved. However, there was a trend towards an improvement in disease related survival only in those patients with more than three nodes involved.     

Adjuvant chemotherapy in nonseminomatous testicular tumour stage II

Preliminary results of a random prospective trial to investigate the necessary extent of adjuvant chemotherapy are presented. Two hundred and sixty-three patients entered the study, of whom 210 (forty-eight stage IIA patients, 162 stage IIB patients) could be evaluated. Two hundred and eight patients are currently free of disease, since three of the five patients with relapses (one stage IIA patient, four stage IIB patients) achieved a complete remission. One IIB patient who had relapsed achieved a partial remission, whereas the final IIB patient who progressed is presently undergoing chemotherapy. One patient died of pneumonia after the first course of VBP. Toxicity consisted mainly of nausea, vomiting and loss of hair, 17% of the patients suffered infection, and 7% experienced sepsis.     

Antiestrogen-cytotoxic chemotherapy and bacillus Calmette-Guerin vaccination in stage II breast cancer: seventy-two-month follow-up

A prospective, randomized clinical trial of adjuvant treatment of 312 stage II breast cancer patients with use of chemotherapy, antiestrogen therapy, and immunotherapy is reported after 72 months of follow-up. The stratification of patients was based on nodal involvement and estrogen receptor (ER) assay of the primary tumors. Findings at 72 months indicate that antiestrogen therapy (tamoxifen, Nolvadex) added to chemotherapy with cyclophosphamide (Cytoxan), methotrexate, and fluorouracil (5-Fluorouracil) (CMF) resulted in significant delayed recurrence in ER-positive postmenopausal patients, ER-positive patients with four or more positive nodes, and ER-positive patients with tumors greater than 3 cm in diameter. The addition of nonspecific immunotherapy with bacillus Calmette-Guerin had no effect on disease-free survival. ER and progesterone receptor measurements in patients with primary breast cancer provide valuable prognostic information on subsequent recurrence and overall survival and should be documented in future clinical trials.     

Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer

Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival.     

Adjuvant CMF chemotherapy in operable breast cancer: Ten years later

This article reports the 10-year results of a trial testing radical mastectomy with or without adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) in 386 women with breast cancer and positive axillary lymph nodes. The long-term analysis confirmed that adjuvant chemotherapy was able to produce a significant relapse-free survival improvement (43.4%) versus control (31.4%,p<0.001) and a trend in total survival (55.2% versus 47.3%,p=0.10). Both relapse-free survival and total survival benefit were significant in premenopausal women. Relapsefree survival was not influenced by drug-induced amenorrhea. In both treatment groups, the results were inversely related to the number of histologically involved axillary nodes. On relapse, salvage treatment applied in the control group failed to produce superior results compared to those achieved in the CMF group and yielded a similar median survival from first relapse between control (37 months) and CMF (32 months) patients. The incidence of severe myelosuppression and hair loss was low (less than 10%) and reversible. Prolonged chemotherapy was not associated with an increased incidence of second neoplasms. We conclude that CMF, as given in this study, was able to improve the course of premenopausal women with high-risk breast cancer during the first decade following radical mastectomy.Resumen En este artículo se informan los resultados de un ensayo de mastectomía radical con o sin terapia adyuvante con CMF (ciclofosfamida, metotrexato y fluoruracilo) en 386 mujeres con cáncer mamario y ganglios axilares positivos. El análisis a largo plazo confirmó que la quimioterapia adyuvante fue capaz de producir una mejoría significativa en la supervivencia libre de recurrencia (43.4%) al confrontarla con el grupo control (31.4%, p<0.001) y una tendencia hacia una mayor supervivencia global (55.2% versus 47.3%, p=0.10). Tanto la supervivencia libre de recurrencia como el beneficio en la supervivencia global fueron de significación en las mujeres premenopáusicas. La supervivencia libre de recurrencia no apareció influenciada por la amenorrea inducida farmacológicamente. En ambos grupos los resultados aparecieron inversamente relacionados con el número de ganglios axilares histológicamente afectados. En presencia de recurrencia de la enfermedad, el tratamiento de salvamiento aplicado al grupo control no produjo mejores resultados que aquellos logrados en el grupo tratado con CMF y resultó en una supervivencia media similar después de la primera recurrencia en las pacientes del grupo control (37 meses) que en las tratadas con CMF (32 meses). La incidencia de mielosupresión severa y de pérdida del cabello fue baja (menos de 10%) y reversible. La quimioterapia prolongada no apareció asociada con una mayor incidencia de segunda neoplasia.Hemos concluído que la CMF, administrada como lo fue en este estudio, fue capaz de mejorar la evolución de las mujeres premenopáusicas con cáncer mamario de alto riesgo en el curso de la primera década después de la mastectomía radical.

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Résumé Cet article relate les résultats à 10 ans d'un essai thérapeutique conduit chez 386 femmes qui présentaient un cancer du sein avec envahissement ganglionnaire axillaire et qui furent traitées par une mastectomie suivie ou non par une chimiothérapie CMF (cyclophosphamide, méthotrexate et fluorouracil). L'analyse à long terme a permis de confirmer que l'adjonction de la chimiothérapie au traitement chirurgical se traduisait par une amélioration significative du taux d'absence de récidive (43,4% contre 31,4% pour le groupe de contrôle,p <0,001), ainsi que par une tendance à l'amélioration du taux de survie (55,2% contre 47,3%,p= 0,10). Soit le taux d'absence de récidive que le taux de survie furent significatifs pour les malades avant la ménopause. Le taux d'absence de récidive ne fut pas influencé par l'aménorrhée provoquée par les agents thérapeutiques. Dans les deux groupes, les résultats furent inversement proportionnels au nombre des ganglions envahis. En cas de récidive, le traitement de souvetage appliqué aux malades du groupe de contrôle n'entraina pas de résultats supérieurs à ceux concernant les malades traités par l'association CMF et se traduisit par une médiane de survie identique dès la première récidive (37 mois pour le groupe contrôle et 32 mois pour le groupe CMF). La fréquence d'une dépression médullaire sévère et de la chute des cheveux fut peu élevée (moins de 10%) et ces phénomènes furent réversibles. La chimiothérapie prolongée ne fut pas suivie par l'augmentation du nombre des cancer secondaires. On peut conclure que, au cours de la décade qui suit la mastectomie radicale, la chimiothérapie avec CMF, ainsi comme fut administrée dans cette étude, améliore l'évolution des cancers du sein à haut risque chez les femmes avant la ménopause.

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Supported in part by contract no. N01-CM-33714 with DCT, NCI, NIH.     

Adjuvant chemotherapy for operable breast cancer in postmenopausal women

Survival figures of women with operable breast cancer reached a plateau 40 years ago. It was only with the advent of adjuvant chemotherapy that these figures showed a dramatic improvement. Data obtained in 105 postmenopausal women with operable breast cancer, treated at our clinic, are presented. Patients with axillary node disease were treated on four different protocols: cyclophosphamide + methotrexate + fluoro-uracil (CMF) with or without immunotherapy was compared with CMF + vincristine + prednisone, while other studies compared observation only with CMF + prednisone and CMF + prednisone + tamoxifen. Patients older than 65 years received tamoxifen or placebo. Patient discriminants and treatment regimens are discussed. Results indicating that certain subsets of postmenopausal women definitely need adjuvant chemotherapy are presented. The literature is briefly reviewed and the motivation for our new studies explained.     

Neoadjuvant chemotherapy in stage III breast cancer

Neoadjuvant chemotherapy in advanced breast cancer can potentially downstage disease prior to definitive surgery. In this study, a doxorubicin-based neoadjuvant regimen was administered to stage III breast cancer patients to assess 1) primary tumor response, 2) tumor involvement of resection margins, and 3) predictive value in cancer outcome. Eighty-two patients with stage IIIA and IIIB breast cancer diagnosed between 1990 and 2003 were studied. All patients received similar chemotherapy regimens, consisting of doxorubicin, cisplatin, and 5-fluorouracil, plus surgery and radiation therapy. End points measured include primary tumor response [complete response (CR) = 100%, partial response (PR) > 50%, or no response (NR) < or = 50%], resection margins for tumor, disease-free, and overall survival. Kaplan-Meier and log-rank tests were performed. Of the 82 patients studied, 34 received neoadjuvant therapy, 48 received conventional postoperative treatment. Seventy-two per cent of the stage IIIB and 22 per cent of the stage IIIA patients received neoadjuvant therapy. In the neoadjuvant group, 29 (85%) patients demonstrated tumor response, 9 (26%) of which were CR. Tumor-free resection margins were achieved in 94 per cent of the neoadjuvant group. Survival analysis demonstrated no benefit comparing neoadjuvant versus postoperative adjuvant therapy but hints at improved disease-free survival in neoadjuvant CR patients (log-rank test, P = 0.07). Eighty-five per cent of patients with stage III breast cancer treated with neoadjuvant chemotherapy experienced clinical response, with 26 per cent CR, and 97 per cent tumor-free resection margins. CR may portend a better cancer outcome.     

Adjuvant chemotherapy for stage C colonic cancer in a multidisciplinary setting

Background: In this study of patients undergoing adjuvant chemotherapy for clinicopathological stage C colonic cancer after optimal surgery, the aims were: to describe their immediate experience of chemotherapy, to assess disease‐free survival, to compare overall survival with that of a matched untreated historical control group, and to evaluate the associations between previously identified adverse risk factors and survival. Methods: Data were drawn from a comprehensive, prospective hospital registry of resections for colorectal cancer between 1971 and 2004, with retrospective data on adjuvant chemotherapy. The main end point was overall survival. Statistical analysis employed the chi‐squared test, Kaplan–Meier estimation and proportional hazards regression. Results: From May 1992 to December 2004, there were 104 patients who received adjuvant chemotherapy. Duration of treatment, withdrawal from treatment, toxicity and other immediate treatment outcomes were similar to those in other equivalent studies. There were no toxicity‐associated deaths. Overall survival was significantly longer in the treated patients than in the control group (3‐year rates 81% and 66%, respectively, P = 0.009). A significant protective effect of adjuvant therapy was found (hazard ratio 0.5, 95% confidence interval 0.3–0.8, P = 0.001) after adjustment for histopathology features previously shown to be negatively associated with survival (high grade, venous invasion, apical node metastasis, free serosal surface involvement). Conclusions: For patients who have had a curative resection for lymph node positive colonic cancer in a specialist colorectal surgical unit and been managed by a multidisciplinary team, post‐operative adjuvant chemotherapy is safe and provides the same survival advantage as seen in randomized trials.     

新辅助化疗及保乳手术在Ⅱ|Ⅲ期乳腺癌中的治疗作用

目的探讨新辅助化疗及保乳手术在Ⅱ,Ⅲ期乳腺癌治疗中的作用。方法对观察组46例Ⅱ,Ⅲ期乳腺癌经新辅助化疗后接受保乳手术治疗的患者进行随访观察,并与59例患者对照研究。新辅助化疗方案为表阿霉素60 mg/m2第1天静脉注射,紫杉醇150 mg/m2。第2天持续3 h静脉滴注,21 d为1个疗程。保乳手术方式为象限切除或肿块局部广泛切除联合腋窝淋巴结清除。对照组常规行根治性切除术。术后对乳房外形及局部复发、远处转移进行随访观察。结果新辅助化疗后,观察组术前肿瘤病灶临床完全缓解(CR)9例,部分缓解(PR)37例。术后病理学检查发现,观察组癌细胞均有不同程度的变性、坏死,细胞间质水肿,纤维增生,炎性细胞浸润;其中病理完全缓解(PCR)4例。对保乳综合治疗(放疗+化疗)结束后1年的31例患者进行外形评估,其中优19.4%(6/31),良58.1%(18/31),差22.6%(7/31)。观察组局部复发率为8.7%(4/46),对照组为6.8%(4/59),两组比较无统计学意义(P0.05);观察组远处转移率为6.5%(3/46),与对照组(15.3%,9/59)比较无统计学意义(P0.05)。结论新辅助化疗后行保乳手术治疗Ⅱ,Ⅲ期乳腺癌基本是安全的,可达到根治性手术的效果。新辅助化疗,规范化切除,术后放疗、化疗是保乳治疗成功的关键。     

Adjuvant chemotherapy and the role of chemotherapy resistance testing for stage I non-small cell lung cancer

The frequency of in vitro chemotherapy resistance in NSCLC is extraordinary: however, its clinical relevance remains unproved. Future studies on the use of the EDR assay and its integration into clinical trials is justified. To achieve the goal "to do no harm", the EDR has a role in eliminating some ineffective agents to avoid unnecessary toxicity, and when possible, in directing therapy. Empiric adjuvant chemotherapy for resected NSCLC may soon become passe as reproducible and generally available molecular testing becomes more common. Profiles from DNA and RNA expression analysis not only help define patients at risk for early recurrence and unresponsiveness to commonly used cytotoxic drugs, but also assist in the development of new assays that are less expensive, reliable, and can be used more commonly than arrays.     

Ⅲ期乳腺癌术前新辅助化疗的临床观察

目的　研究Ⅲ期乳腺癌术前新辅助化疗的临床效果。方法　 1999年～ 2 0 0 1年 6月住院手术治疗的Ш期乳腺癌患者 62例 ,术前行辅助化疗 ,回顾分析 1997～ 1998年间收治的 3 7例Ш期乳腺癌未作辅助化疗而直接手术作为对照组。从手术切除后病理切片观察细胞变化及术后局部复发 ,远处转移等方面进行比较。结果　手术后病理切片观察癌细胞坏死情况 ,新辅助化疗组有效率为 67.7% ,而对照组仅 6例癌细胞有轻度局灶坏死。术后三年局部复发或远处转移新辅助化疗组为 11.4% ,对照组 2 4.3 %。结论　手术前辅助化疗能大量杀伤肿瘤细胞 ,缩小肿瘤便于手术 ,减少远处播散机会     

Assessment of response to preoperative chemotherapy in patients with stage II and III breast cancer: the value of MRI

The response to preoperative chemotherapy in breast cancer was assessed by magnetic resonance imaging (MRI), and compared to the histological and clinical findings.Forty-two patients with stage II and III breast carcinoma were evaluated prospectively prior to and after preoperative chemotherapy by MRI, clinical and histological examination. Radiological response was assessed using the MRI parameters: total tumor volume (TTV), maximum enhancement index (MEI) and their product (TTV^*MEI).A significant reduction in all MRI parameters was observed after chemotherapy. Overall clinical and radiological response rates were comparable (69% vs 73%). MRI was not useful for the prediction of complete pathologic response. A fair correlation between TTV postchemotherapy and final histological diameter was found. A significant difference of residual TTV for patients undergoing breast conservative surgery vs mastectomy was observed.Conclusion: MRI can demonstrate responses induced by preoperative chemotherapy in breast cancer, but it cannot determine complete pathologic responses.     

Surgical conservation planning after neoadjuvant chemotherapy for stage II and operable stage III breast carcinoma

BACKGROUND: This study was performed to investigate the extent of tumor downstaging achieved in women with operable breast cancer treated with neoadjuvant chemotherapy and breast-conservation surgery, develop recommendations for effective surgical planning, and report local-regional recurrence rates with this approach. METHODS: One hundred nine patients with stage II or III (T3N1) breast cancer were treated in three prospective trials utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC, n = 72) or paclitaxel (n = 37) followed by segmental resection (n = 109) and axillary node dissection (n = 94). Postoperatively, patients received 4 additional cycles of FAC followed by irradiation of the breast. The median follow-up was 53 months. RESULTS: The median tumor size was 4 cm (range 1.1 to 9 cm) at presentation and only 1 cm (range 0 to 4.5 cm) after four cycles of chemotherapy. The primary tumor could not be palpated after chemotherapy in 55% of 104 patients presenting with a palpable mass and therefore required needle localization or ultrasound guidance for surgical resection. Of the 34 patients clinically deemed to have no residual carcinoma in the breast after chemotherapy and before surgery, only 50% of these patients were found to have no residual carcinoma on pathologic examination after surgery. Patients with primary tumors < or =2 cm were significantly more likely than patients with larger tumors to have complete eradication of the primary tumor prior to surgery (P <0.001). The 5-year local-regional recurrence rate was 5%. CONCLUSIONS: Tumor downstaging is marked in patients with operable breast cancer and requires close monitoring during chemotherapy. We recommend placement of metallic tumor markers when the primary tumor is < or =2 cm to facilitate adequate resection and pathologic processing. Resection of the tumor bed remains necessary in women deemed to have a complete clinical response to ensure low rates of recurrence.     

Tamoxifen versus chemotherapy as adjuvant treatment in stage III breast cancer

A randomized prospective trial was conducted to compare Tamoxifen and combination chemotherapy (5-fluorouracil, doxorubicin and cyclophosphamide) as adjuvant treatment for patients with locally advanced (Stage III) breast cancer. At the end of 5 years, no significant difference could be found in the disease-free period for both groups.     

Adjuvant chemotherapy after surgery and radiation for stage III and IV head and neck cancer.

Twenty consecutive patients with Stage III and IV squamous head and neck cancer were treated with surgery, radiation, and adjuvant multiagent chemotherapy. Eleven other patients who were referred for local recurrent disease were treated with second surgery or radiation and also with adjuvant chemotherapy. The actuarial survival of these two groups of patients combined (N = 31) was 87% at 6 years. Four patients died of recurrent cancer (two in each group), six of unrelated causes during a 6-year follow-up. The side effects of adjuvant chemotherapy were mild to moderate and of short duration.     

Continuous infusional combination chemotherapy in inflammatory breast cancer: a phase II study

Despite the introduction of systemic chemotherapy, inflammatory breast cancer (IBC) remains a disease with a poor prognosis. We performed this phase II study to evaluate the efficacy of infusional chemotherapy as initial treatment in patients with IBC. Fifty-four patients with newly diagnosed IBC were offered infusional chemotherapy and 34 accepted. The schedule consisted of continuous infusional ECF (bolus epirubicin and cisplatin, substituted by carboplatin or cyclophosphamide in some patients) plus continuous 5-FU, given three weekly for six cycles. Following chemotherapy patients went on to have surgery and/or radiotherapy. The chemotherapy was well tolerated and resulted in an overall response rate of 79% with 35% of patients achieving a complete clinical response. The median response duration, time to progression and overall survival were 12 months (4-89+ months), 12 months (4-89+ months) and 23 months (7-89+ months), respectively. Patients had a 5 year disease free and overall survival of 11% and 29%, respectively. Infusional ECF is well tolerated and achieves a high clinical response rate in patients with IBC, but survival results do not appear to be superior to those achieved with conventional bolus chemotherapy schedules.