ABSTRACT
PURPOSE: To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). PATIENTS AND METHODS: Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. RESULTS: One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. CONCLUSION: VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Chemotherapy, Adjuvant , Disease Progression , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Middle Aged , Neoplasm Staging , Treatment Outcome , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/therapeutic use , VinorelbineABSTRACT
PURPOSE: We conducted this study to evaluate the efficacy and toxicity of fractionated high-dose cisplatin as neoadjuvant organ-preserving chemotherapy, followed by definitive radiotherapy, for untreated and advanced squamous cell carcinoma of the larynx. MATERIALS AND METHODS: From August 1990 to April 1994, 32 patients bearing previously untreated advanced squamous cell carcinoma of the larynx (12 stage III and 20 stage IV) received three courses of high-dose cisplatin (100 mg/m2 on day 1 and day 8 every 28 days) before definitive external radiation therapy with 65 to 70 Gy (180-200 cGy daily for 6-8 weeks). Twenty-eight patients were men; median age was 57 years (range, 31-69); and median performance status (ECOG) was 1 (0-2). RESULTS: With an average follow-up time of 18 months (range, 6-47), 30 patients are evaluable for response and 32 for toxicity. Responses after three courses of chemotherapy were: complete response, 18 patients (60%), and partial response, 7 patients (23%), for an overall response rate of 83%. Only one patient showed progressive disease. Fifteen patients (50%; 12 complete and 3 partial responders) had pathologic complete remission. Eighty percent of patients had no evidence of disease after the therapeutic program. Median disease-free survival was 24 months, and median overall survival was 28 months (range, 6-47). Overall, in 46% of all evaluable patients, organ preservation with acceptable function was achieved. Disease-free survival and larynx preservation were strongly correlated with pathologic complete remission. The average dose intensity received at the end of the third course of therapy was 47 mg/m2/week. There were no drug-related deaths. The main acute toxicity was grade 2-3 nausea and vomiting in 75% of patients. Two patients developed renal impairment after the first course of cisplatin. Ototoxicity (grade 2-3) was seen in 43% of patients, and peripheral neuropathy (grade 2-3) was observed in 12% of patients. In contrast, myelotoxicity and mucositis were mild. CONCLUSION: In conclusion, this strategy with fractionated high-dose cisplatin given on an outpatient basis is an attractive approach that produces a high rate of complete response and larynx preservation with an advantageous toxicity profile.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Laryngeal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/adverse effects , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/adverse effects , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/radiotherapy , Male , Middle Aged , Neoadjuvant Therapy , Survival Analysis , Treatment OutcomeABSTRACT
Between October 1986 and August 1988, 33 previously untreated patients with locally advanced cervical carcinoma were studied to evaluate the efficacy and toxicity of a neoadjuvant chemotherapy combination consisting of cisplatin 50 mg/m2 intravenously (IV) on day 1, vincristine 1.4 mg/m2 IV on day 1, and bleomycin 25 mg/m2 IV in a 6-hour infusion on days 1-3. Cycles were repeated every 10 days for a total of three cycles, after which definitive radiation therapy (external and intracavitary) was administered. The median age was 47 years, and distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 12 subjects; IIIB, 19; and IVA, two. A multidisciplinary team conducted both staging and assessment of response to induction chemotherapy before the beginning of radiotherapy. Thirty-one women were fully evaluable for response and toxicity. No complete response was observed; seven subjects (23%) experienced a partial response, 18 (58%) had no change, and six (19%) showed progressive disease. Toxicity was mild to moderate and included nausea and vomiting, alopecia, hyperthermia, peripheral neurotoxicity, and anemia. We conclude that this regimen at this dosage and time interval produced a low number of objective regressions with a significant progression rate and is of doubtful value as neoadjuvant chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Middle Aged , Vincristine/administration & dosageABSTRACT
Se revisaron las historias clínicas de 44 pacientes con diagnóstico de seminoma puro de testículo tratados entre 1981 y 1989. Veintiún pacientes (48%) fueron clasificados como estadio Iñ 16 pacientes (36%) como estadio IIAñ 4 pacientes (9%) estadio IIB y 3 pacientes (7%) estadio III. Tenían antecedentes de criptorquidia 7 pacientes (16%); de traumatismo testicular 9 pacientes (20%); orquiepididimitis 1 paciente (2%) y de malformación del aparato urogenital 1 pacientes (2%). El seminoma era típico en 43 pacientes (98%) y de variedad anaplásica en el paciente restante (2%). No hobu casos de seminoma espermatocítico. En 6 pacientes (14%) se halló un invel elevado de subunidad beta de gonadotropina coriónica humana persistente luego de la orquiectomía. Se identificaron en 2 de ellos células gigantes del sinciciotrofoblasto por medio de cortes seriados del espécimen quirúrgico. En todos los casos los niveles de este marcador sérico retornaron a valores normales luego del tratamiento primario radiante y/o quimioterápico. La sobrevida global para la totalidad de los pacientes es 96% a 8 años. Esto corresponde a un 100% para estadios I, IIA y IIB y 33% (1/3) para estadio III. No hubo fallas al tratamiento dentro de los campos de irradiación. Solamente 2 pacientes (5%) presentaron enfermedad recurrente en territorios extralinfáticos. Ambos fueron tratados exitosamente. La terapia fue en general bien tolerada y la toxicidad fue leve a moderada
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Dysgerminoma/radiotherapy , Testicular Neoplasms/radiotherapy , Combined Modality Therapy , Dysgerminoma/pathology , Dysgerminoma/therapy , Follow-Up Studies , Neoplasm Staging , Orchiectomy , Retrospective Studies , Testicular Neoplasms/pathology , Testicular Neoplasms/therapyABSTRACT
Se revisaron las historias clínicas de 44 pacientes con diagnóstico de seminoma puro de testículo tratados entre 1981 y 1989. Veintiún pacientes (48%) fueron clasificados como estadio Iñ 16 pacientes (36%) como estadio IIAñ 4 pacientes (9%) estadio IIB y 3 pacientes (7%) estadio III. Tenían antecedentes de criptorquidia 7 pacientes (16%); de traumatismo testicular 9 pacientes (20%); orquiepididimitis 1 paciente (2%) y de malformación del aparato urogenital 1 pacientes (2%). El seminoma era típico en 43 pacientes (98%) y de variedad anaplásica en el paciente restante (2%). No hobu casos de seminoma espermatocítico. En 6 pacientes (14%) se halló un invel elevado de subunidad beta de gonadotropina coriónica humana persistente luego de la orquiectomía. Se identificaron en 2 de ellos células gigantes del sinciciotrofoblasto por medio de cortes seriados del espécimen quirúrgico. En todos los casos los niveles de este marcador sérico retornaron a valores normales luego del tratamiento primario radiante y/o quimioterápico. La sobrevida global para la totalidad de los pacientes es 96% a 8 años. Esto corresponde a un 100% para estadios I, IIA y IIB y 33% (1/3) para estadio III. No hubo fallas al tratamiento dentro de los campos de irradiación. Solamente 2 pacientes (5%) presentaron enfermedad recurrente en territorios extralinfáticos. Ambos fueron tratados exitosamente. La terapia fue en general bien tolerada y la toxicidad fue leve a moderada (AU)
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Dysgerminoma/radiotherapy , Testicular Neoplasms/radiotherapy , Dysgerminoma/pathology , Dysgerminoma/therapy , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy , Follow-Up Studies , Neoplasm Staging , Retrospective Studies , Orchiectomy , Combined Modality TherapyABSTRACT
The records of 44 patients with pure testicular seminoma treated from 1981 to 1989 were reviewed. Twenty-one patients (48%) had stage I disease; 16 patients (36%) stage IIA; 4 patients (9%) stage IIB and 3 patients (7%) stage III. A previous history of cryptorchism was present in 7 patients (16%); testicular trauma in 9 patients (20%); orchiepididymits in 1 patient (2%) and genitourinary malformation in 1 patient (2%). Typical seminoma was observed in 43 patients (98%) and anaplastic seminoma in the remaining one (2%). There were no patients with spermatocytic seminoma. An elevated level of beta-human chorionic gonadotropin persisting after orchiectomy was found in 6 patients (14%). Syncytiotrophoblastic giant cells were identified after serial sections of the surgically resected tissue in two patients. Levels of this serum marker returned to normal values after primary treatment in all patients. Overall survival for all patients is 96% at 8 years. This corresponds to 100% for stages I, IIA and IIB and to 33% (1/3) for state III. Two patients (5%) presented recurrent disease in extralymphatic territories. Both of them were successfully rescued with proper therapy. Treatment was generally well tolerated and toxicity was mild to moderate.
Subject(s)
Dysgerminoma/radiotherapy , Testicular Neoplasms/radiotherapy , Adolescent , Adult , Combined Modality Therapy , Dysgerminoma/pathology , Dysgerminoma/therapy , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Orchiectomy , Retrospective Studies , Testicular Neoplasms/pathology , Testicular Neoplasms/therapyABSTRACT
The records of 44 patients with pure testicular seminoma treated from 1981 to 1989 were reviewed. Twenty-one patients (48
) had stage I disease; 16 patients (36
) stage IIA; 4 patients (9
) stage IIB and 3 patients (7
) stage III. A previous history of cryptorchism was present in 7 patients (16
); testicular trauma in 9 patients (20
); orchiepididymits in 1 patient (2
) and genitourinary malformation in 1 patient (2
). Typical seminoma was observed in 43 patients (98
) and anaplastic seminoma in the remaining one (2
). There were no patients with spermatocytic seminoma. An elevated level of beta-human chorionic gonadotropin persisting after orchiectomy was found in 6 patients (14
). Syncytiotrophoblastic giant cells were identified after serial sections of the surgically resected tissue in two patients. Levels of this serum marker returned to normal values after primary treatment in all patients. Overall survival for all patients is 96
at 8 years. This corresponds to 100
for stages I, IIA and IIB and to 33
(1/3) for state III. Two patients (5
) presented recurrent disease in extralymphatic territories. Both of them were successfully rescued with proper therapy. Treatment was generally well tolerated and toxicity was mild to moderate.
