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1.
Ann Oncol ; 21(2): 342-347, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19892746

ABSTRACT

BACKGROUND: Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III-IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. RESULTS: Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m(2) (n = 3) and 30 mg/m(2) (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. CONCLUSIONS: Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Neoplasms, Squamous Cell/drug therapy , Neoplasms, Squamous Cell/radiotherapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Combined Modality Therapy/adverse effects , Disease Progression , Dose-Response Relationship, Drug , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Panitumumab , Patient Compliance , Radiotherapy, Intensity-Modulated/adverse effects , Treatment Outcome
2.
Appl Radiat Isot ; 61(5): 1075-81, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15308195

ABSTRACT

A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m(2) body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBEGy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBEGy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBEGy (median 57.8 RBEGy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBEGy.


Subject(s)
Boron Neutron Capture Therapy/methods , Brain Neoplasms/radiotherapy , Fructose/analogs & derivatives , Glioblastoma/radiotherapy , Radiotherapy Planning, Computer-Assisted/statistics & numerical data , Aged , Boron/blood , Boron Compounds/therapeutic use , Boron Neutron Capture Therapy/statistics & numerical data , Brain Neoplasms/blood , Fast Neutrons/therapeutic use , Female , Fructose/therapeutic use , Glioblastoma/blood , Humans , Male , Middle Aged , Monte Carlo Method , Radiotherapy Dosage
3.
J Neurooncol ; 62(1-2): 171-86, 2003.
Article in English | MEDLINE | ID: mdl-12749712

ABSTRACT

A two-compartment open model has been developed for predicting 10B concentrations in blood following intravenous infusion of the L-p-boronophenylalanine-fructose complex in humans and derived from pharmacokinetic studies of 24 patients in Phase I clinical trials of boron neutron capture therapy. The 10B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biexponential disposition profile with harmonic mean half-lives of 0.32 +/- 0.08 and 8.2 +/- 2.7 h, most likely due to redistribution and primarily renal elimination, respectively. The mean model rate constants k12, k21, and k10 are (mean +/- SD) 0.0227 +/- 0.0064 min(-1), 0.0099 +/- 0.0027 min(-1), 0.0052 +/- 0.0016 min(-1), respectively, and the central compartment volume of distribution V1 is 0.235 +/- 0.042 L/kg. In anticipation of the initiation of clinical trials using an intense neutron beam with concomitantly short irradiations, the ability of this model to predict, in advance, the average blood 10B concentration during brief irradiations was simulated in a retrospective analysis of the pharmacokinetic data from these patients. The prediction error for blood boron concentration and its effect on simulated dose delivered for each irradiation field are reported for three different prediction strategies. In this simulation, error in delivered dose (or, equivalently, neutron fluence) for a given single irradiation field resulting from error in predicted blood 10B concentration was limited to less than 10%. In practice, lower dose errors can be achieved by delivering each field in two fractions (on two separate days) and by adjusting the second fraction's dose to offset error in the first.


Subject(s)
Boron Compounds/pharmacokinetics , Boron/blood , Boron/analysis , Boron Neutron Capture Therapy/methods , Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Glioblastoma/radiotherapy , Half-Life , Humans , Melanoma/radiotherapy , Models, Theoretical , Predictive Value of Tests , Radiotherapy Dosage , Skin Neoplasms/radiotherapy
4.
Radiat Res ; 155(4): 611-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11260663

ABSTRACT

An open two-compartment model has been developed for predicting (10)B concentrations in blood after intravenous infusion of the l-p-boronophenylalanine-fructose complex (BPA-F) in humans and derived from studies of pharmacokinetics in 24 patients in the Harvard-MIT Phase I clinical trials of BNCT. The (10)B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biphasic exponential clearance profile with half-lives of 0.34 +/- 0.12 and 9.0 +/- 2.7 h, due to redistribution and primarily renal elimination, respectively. The model rate constants k(1), k(2) and k(3) are 0.0227 +/- 0.0064, 0.0099 +/- 0.0027 and 0.0052 +/- 0.0016 min(-1), respectively, and the central compartment volume of distribution, V(1), is 0.235 +/- 0.042 kg/kg. The validity of this model was demonstrated by successfully predicting the average pharmacokinetic response for a cohort of patients who were administered BPA-F using an infusion schedule different from those used to derive the parameters of the model. Furthermore, the mean parameters of the model do not differ for cohorts of patients infused using different schedules.


Subject(s)
Boron Compounds/pharmacokinetics , Boron/pharmacokinetics , Fructose/pharmacokinetics , Models, Biological , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacokinetics , Adult , Aged , Boron/blood , Boron Compounds/administration & dosage , Boron Neutron Capture Therapy , Brain Neoplasms/blood , Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Female , Glioblastoma/blood , Glioblastoma/radiotherapy , Humans , Infusions, Intravenous , Male , Melanoma/blood , Melanoma/radiotherapy , Melanoma/secondary , Middle Aged , Phenylalanine/administration & dosage , Skin Neoplasms/blood , Skin Neoplasms/radiotherapy
5.
Int J Radiat Oncol Biol Phys ; 43(5): 1001-8, 1999 Mar 15.
Article in English | MEDLINE | ID: mdl-10192347

ABSTRACT

BACKGROUND: Combined modality therapy plays a central role in the management of head and neck malignancies. This study examined the feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel (Taxol) and radiation therapy. METHODS: Fourteen patients with a median age of 56 years (range 42-81) were treated. Paclitaxel was given every 3 weeks at a dose of 100 mg/m2 concurrently with external beam radiation. The patients treated included those who had failed to achieve a complete response (CR) to induction chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had locally advanced disease not previously treated. RESULTS: Median follow-up from the initiation of treatment is 40 months (range 23-48). The majority of patients (13/14) achieved clinical CRs at the primary site. The development of responses was characterized by a long time course. Three patients who were nonresponders (NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the primary site, one did not achieve a CR, and the other had residual disease in the neck. Four patients have failed, one with local-regional disease, one with a marginal failure, one with distant metastases, and one was not rendered disease-free by the treatment. As expected, significant local toxicity was observed. Most patients were managed with the aid of a percutaneous endoscopic gastrostomy (PEG). Two patients experienced significant moist desquamation and required treatment breaks of greater than 1 week. CONCLUSION: Paclitaxel can be given on a 3-week schedule at 100 mg/m2 concurrently with radiation. The preliminary results indicate good local responses and acceptable toxicity. This treatment approach merits further study in the treatment of head and neck malignancies, and should be considered as an option in other sites.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Paclitaxel/therapeutic use , Radiation-Sensitizing Agents/therapeutic use , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Radiotherapy Dosage , Remission Induction , Treatment Failure
6.
Semin Surg Oncol ; 15(2): 120-5, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9730418

ABSTRACT

Induction, or preoperative therapy for rectal carcinoma, is a controversial topic which appears to have clinical utility in a number of distinct settings that range from early stage to locally advanced disease. Common to all treatment scenarios is the intent of reducing the likelihood of recurrence in the pelvis following surgery. An additional and evolving role is a reduction in the extent of surgery following a complete or partial clinical response to the induction regimen. While radiation as a single modality can lead to downstaging and, perhaps, a reduction in local recurrence, combined modality with 5-fluorouracil (5-FU) and radiation appears to have a greater therapeutic benefit that may be further enhanced by the administration of leucovorin.


Subject(s)
Antidotes/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Carcinoma/drug therapy , Carcinoma/radiotherapy , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Combined Modality Therapy , Humans , Neoplasm Staging , Preoperative Care , Rectal Neoplasms/pathology
7.
J Clin Oncol ; 16(4): 1331-9, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9552034

ABSTRACT

PURPOSE: A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed. RESULTS: Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor. CONCLUSION: TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Taxoids , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Docetaxel , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/therapeutic use , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Paclitaxel/analogs & derivatives , Paclitaxel/therapeutic use
8.
Int J Radiat Oncol Biol Phys ; 39(4): 915-20, 1997 Nov 01.
Article in English | MEDLINE | ID: mdl-9369141

ABSTRACT

PURPOSE: To determine the risk of nodal failure in patients with early-stage invasive breast cancer with clinically negative axillary lymph nodes treated with two-field tangential breast irradiation alone, without axillary lymph node dissection or use of a third nodal field. METHODS AND MATERIALS: Between 1988 and 1993, 986 evaluable women with clinical Stage I or II invasive breast cancer were treated with breast-conserving surgery and radiation therapy. Of these, 92 patients with clinically negative nodes received tangential breast irradiation (median dose, 45 Gy) followed by a boost, without axillary dissection. The median age was 69 years (range, 49-87). Eighty-three percent had T1 tumors. Fifty-three patients received tamoxifen, 1 received chemotherapy, and 2 patients received both. Median follow-up time for the 79 survivors was 50 months (range, 15-96). Three patients (3%) have been lost to follow-up after 20-32 months. RESULTS: No isolated regional nodal failures were identified. Two patients developed recurrence in the breast only (one of whom had a single positive axillary node found pathologically after mastectomy). One patient developed simultaneous local and distant failures, and six patients developed distant failures only. One patient developed a contralateral ductal carcinoma in situ, and two patients developed other cancers. CONCLUSION: Among a group of 92 patients with early-stage breast cancer (typically T1 and also typically elderly) treated with tangential breast irradiation alone without axillary dissection, with or without systemic therapy, there were no isolated axillary or supraclavicular regional failures. These results suggest that it is feasible to treat selected clinically node-negative patients with tangential fields alone. Prospective studies of this approach are warranted.


Subject(s)
Breast Neoplasms/radiotherapy , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Middle Aged , Neoplasm Staging , Tamoxifen/therapeutic use , Treatment Outcome
9.
J Clin Oncol ; 15(9): 3100-10, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9294473

ABSTRACT

PURPOSE: A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). PATIENTS AND METHODS: One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. RESULTS: Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. CONCLUSION: PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Head and Neck Neoplasms/pathology , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Remission Induction , Survival Analysis , Treatment Outcome
10.
Int J Radiat Oncol Biol Phys ; 38(4): 777-83, 1997 Jul 01.
Article in English | MEDLINE | ID: mdl-9240646

ABSTRACT

PURPOSE: To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS: Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS: Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION: Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.


Subject(s)
Colonic Neoplasms/radiotherapy , Colonic Neoplasms/surgery , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Adult , Aged , Colonic Neoplasms/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm, Residual , Rectal Neoplasms/pathology
11.
Cancer ; 79(4): 671-83, 1997 Feb 15.
Article in English | MEDLINE | ID: mdl-9024704

ABSTRACT

BACKGROUND: There has been increasing interest in the use of sphincter-preserving therapy for patients with distal rectal carcinomas. The outcomes of conservative treatments for early stage rectal carcinoma appear to be comparable to that achieved with abdominoperineal resection. METHODS: Retrospective and prospective clinical series of patients with distal rectal carcinoma treated by local excision alone, local excision with postoperative adjuvant therapy, preoperative radiation followed by local excision, or radical circumferential sphincter-sparing surgeries were reviewed. The local control rates, salvage rates, and treatment complications in patients treated by these various methods were examined. RESULTS: Patients with T1 distal rectal carcinoma with favorable clinical and histopathologic characteristics treated with local excision alone had a local control rate of greater than 90% in most series. Postoperative chemoradiation improved local control for those with T1 disease with unfavorable characteristics, or those with T2 disease. Most T3 patients had failure rates of greater than 30% despite adjuvant local and systemic therapy. With high dose preoperative radiation, approximately 80% of patients with locally advanced or unresectable tumors were able to undergo sphincter-preservation treatment. CONCLUSIONS: Patients with favorable T1 rectal carcinoma are likely to be adequately treated with local excision alone. Patients with T1 disease with unfavorable characteristics as well as T2 patients will benefit from postoperative chemoradiation. The use of local therapy in T3 patients needs to be carefully considered because these patients are at relatively high risk for local recurrence despite adjuvant therapy. Preoperative radiation followed by either local excision or radical circumferential sphincter-sparing resections appears promising in allowing sphincter preservation in patients with locally advanced tumors.


Subject(s)
Rectal Neoplasms/surgery , Rectum/surgery , Combined Modality Therapy , Humans , Lymphatic Metastasis , Methods , Prospective Studies , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Retrospective Studies
12.
J Clin Oncol ; 14(5): 1672-8, 1996 May.
Article in English | MEDLINE | ID: mdl-8622087

ABSTRACT

PURPOSE: We conducted a phase II study designed to evaluate the activity, safety, and tolerability of docetaxel (Taxotere: Rhône-Poulenc Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who had not received prior palliative chemotherapy. PATIENTS AND METHODS: Thirty-one patients with measurable, locoregional, or metastatic SCCHN were treated with docetaxel, administered at a dose of 100 mg/m2 as a 1-hour intravenous (i.v.) infusion once every 21 days on an outpatient basis. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic administration of growth factors or antiemetics was not permitted. RESULTS: Thirty-one patients were treated. Twenty-nine patients were assessable for response and 30 for toxicity. Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response had stable disease (SD) and seven (23%) experienced progression of disease (PD). The major response rate was 42% (95% confidence interval [CI], 24% to 60%). The median duration of responses was 5 months (range, 2 to 14). The principal toxicity was leukopenia, which occurred with rapid onset and brief duration. Sixteen patients (53%) experienced nadir fever, and 13 required dose reduction. Hypersensitivity reactions occurred in four patients. Grade 3 peripheral neuropathy occurred in two patients; grade 2 or 3 fatigue occurred in six (20%) and 10 (33%), respectively. Minimal edema (grade 1) occurred in five patients (17%). Clinically significant mucositis, diarrhea, or dermatitis were not observed. CONCLUSION: Docetaxel has major activity against SCCHN. It appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis. Premedication with dexamethasone, cimetidine, and diphenhydramine is associated with a reduced incidence of significant edema, hypersensitivity reactions, and dermatologic toxicities.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/adverse effects , Docetaxel , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/adverse effects , Paclitaxel/therapeutic use , Treatment Outcome
13.
Int J Radiat Oncol Biol Phys ; 29(3): 535-40, 1994 Jun 15.
Article in English | MEDLINE | ID: mdl-8005812

ABSTRACT

PURPOSE: To investigate whether etanidazole and cisplatin can be given safely together and to evaluate the relationship between incidence of peripheral neuropathy and cumulative exposure to etanidazole and cisplatin, as well as other toxicities and treatment outcome. METHODS AND MATERIALS: Thirty-two previously untreated patients with locally advanced esophageal cancer were entered on a Phase I study of etanidazole combined with radiation therapy and chemotherapy. Cisplatin/5-FU (two cycles, weeks 1 and 4) and etanidazole (weeks 2, 3 and 5) were given concurrently with radiation therapy. Eligible patients then underwent surgical resection. All patients were scheduled to receive two additional cycles of cisplatin/5-FU chemotherapy after completion of radiation therapy (definitive arm) or surgery (preoperative arm). RESULTS: Of 19 fully evaluable patients, nine (47%) developed peripheral neuropathy. Six of six patients, 65 years or older, experienced peripheral neuropathy, compared with three of 13 patients less than 65 years old (p = .003). For patients younger than 65 years, two of the two patients with single dose area under the curve (AUC) > 4.0 mMhr experienced peripheral neuropathy, compared with one of 11 patients with single-dose AUC < 4.0 mMhr (p = .03). Grade 4 toxicity included neutropenia (23%) and thrombocytopenia (26%). No other Grade 4 toxicity was observed. The pathologic complete response rate in patients who underwent surgical resection was 29%. CONCLUSION: This regime of chemotherapy, radiotherapy, and etanidazole had acceptable toxicity. However, combining etanidazole and cisplatin appears to increase the risk of developing peripheral neuropathy for at least some categories of patients. Further studies of these interactions are needed.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Etanidazole/adverse effects , Peripheral Nervous System Diseases/chemically induced , Adult , Aged , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Etanidazole/administration & dosage , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Middle Aged , Treatment Outcome
14.
Head Neck ; 15(5): 413-8, 1993.
Article in English | MEDLINE | ID: mdl-8407313

ABSTRACT

A phase II clinical trial was initiated in 1987 to evaluate a new induction regimen of cis-platinum, 5-fluorouracil, and leucovorin (PFL) for patients with stages III-IV squamous cell carcinoma of the head and neck. Ninety patients were treated and followed for a median duration of 18 months. The median age was 55 and 87% of the patients had stage IV disease. The rates of complete and overall clinical response following three cycles of PFL were 57% and 80%, respectively; the rate of complete response at the primary site was 72%. Eighty-four percent of patients were treated to the primary site with radiation alone (median dose 68 Gy in daily 1.8-Gy fractions) irrespective of the location of the primary site or initial T-stage. The acute tolerance to full-course radiation following PFL was acceptable. The actuarial rate of primary site control for patients treated with radiation was 67% at 36 months. An important prognostic indicator for primary site control was a complete clinical response to induction PFL. For patients who achieved a complete response, radiation or surgery followed by radiation controlled primary site disease equally well at 70%. Patients with a partial response did less well. For these patients, surgery and radiation appeared slightly better than radiation alone.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Fluorouracil/administration & dosage , Head and Neck Neoplasms/drug therapy , Leucovorin/administration & dosage , Actuarial Analysis , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Follow-Up Studies , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Humans , Lymph Node Excision , Middle Aged , Neoplasm Staging , Radiotherapy Dosage , Remission Induction , Survival Rate , Treatment Outcome
15.
Semin Surg Oncol ; 9(1): 3-13, 1993.
Article in English | MEDLINE | ID: mdl-8356382

ABSTRACT

Chemotherapy, as preliminary treatment before surgery and/or radiation for advanced squamous cell carcinoma of the head and neck, is no longer novel. In prospective trials to date, however, multiple agent induction chemotherapy has yet to demonstrate the initial presumptive promise of improved rates of cure. As an alternate goal, there has emerged a renewed attentiveness toward limiting treatment morbidity, several strategies for which may be considered. Extirpative, often radical, surgery on the primary site of disease usually represents the most significant threat to life quality. Various ways of limiting surgical morbidity will be considered by way of introduction. The trends of head and neck cancer treatment over the decades, leading into the era of induction chemotherapy and refined radiation techniques, will be described. At the combined Dana-Farber/New England Deaconess Head and Neck Oncology Clinic, an experience with over 300 patients receiving induction chemotherapy for advanced head and neck cancer has been analyzed with an emphasis on the postulate of lessening the extent of surgery in appropriately selected patients. In a comparison between trials initiated in 1980 and 1987, improved complete response rates from 26 to 57% were documented. Survival rates were identical, but the use of planned primary site ablative surgery was decreased from 47 to 14%. While some increase in local failure has been noted in patients treated by primary site radiation alone, surgical salvage appeared to be more effective. The implication of these trends for patterns of failure and surgical salvage and data concerning the need for neck dissection in this group of patients will be briefly summarized. Other trials addressing organ-preservation strategies will also be referenced and the dichotomy between survival-based studies and morbidity-limiting studies illustrated. Independent trends in radiation technique as a potential substitute for traditional surgical practice will be reviewed.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Salvage Therapy
16.
Semin Surg Oncol ; 9(1): 46-50, 1993.
Article in English | MEDLINE | ID: mdl-8356385

ABSTRACT

The treatment of locally advanced rectal carcinoma is one of the more complicated problems in the management of colorectal carcinoma. More than any other site successful treatment requires a multimodality approach as surgery alone is frequently insufficient to completely eradicate all disease. This review focuses primarily on the management of patients who present without prior treatment and discusses the role of preoperative radiation therapy as well as intraoperative radiation therapy. Although much less gratifying, patients who present after failing previous therapy may also benefit from an aggressive multimodality approach.


Subject(s)
Carcinoma/surgery , Rectal Neoplasms/surgery , Carcinoma/pathology , Carcinoma/radiotherapy , Combined Modality Therapy , Humans , Intraoperative Care , Neoplasm Staging , Preoperative Care , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy
17.
World J Surg ; 15(3): 352-6, 1991.
Article in English | MEDLINE | ID: mdl-1853614

ABSTRACT

The recognition of a high incidence of local failure following surgical management of adenocarcinoma of the gallbladder has led to the use of adjuvant radiation therapy. In order to deliver higher doses to the gallbladder bed, intraoperative radiation therapy (IORT) has been used both with and without external beam radiation. The experience to date is reviewed. Ten patients have been treated, all of whom had either gross residual or unresected disease. The median survival for the group was approximately 1 year. There were no long-term survivors. The IORT did not contribute to the overall morbidity. Because of the limited number of patients and the advanced nature of the disease, the role of IORT in the management of gallbladder carcinoma has yet to be determined. The utility of this modality will most likely reside in the treatment of minimal residual disease at the time of cholecystectomy rather than in the palliative treatment of unresectable tumors.


Subject(s)
Adenocarcinoma/radiotherapy , Gallbladder Neoplasms/radiotherapy , Adenocarcinoma/surgery , Aged , Combined Modality Therapy , Gallbladder Neoplasms/surgery , Humans , Intraoperative Period , Middle Aged , Radiotherapy/adverse effects , Radiotherapy Dosage
18.
Ann Intern Med ; 112(3): 167-72, 1990 Feb 01.
Article in English | MEDLINE | ID: mdl-2297193

ABSTRACT

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Drug Administration Schedule , Drug Evaluation , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Leucovorin/administration & dosage , Leucovorin/blood , Male , Middle Aged , Neoplasm Staging , Tetrahydrofolates/blood
19.
Surgery ; 105(6): 724-33, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2727900

ABSTRACT

The results of a 5-year experience with use of intraoperative radiation therapy (IORT) in the management of locally advanced bile duct carcinoma are presented. Fifteen patients received IORT doses between 5 and 20 Gy for localized disease, which was either primary and resected with microscopic residual (2 patients), primary and unresected (10 patients), or recurrent (3 patients). Thirteen patients also received postoperative radiation therapy. The median survival of the 12 patients with primary disease was 14 months, with disease controlled in the porta hepatis in 5 of 10 evaluable patients. The three patients with recurrent disease survived 2, 9, and 11 months. There were two operative deaths, for an operative mortality of 13%. Acute and chronic complications are reviewed. Cholangitis is the most frequent in both categories. This aggressive approach in the therapy for advanced disease has an acceptable level of morbidity and may warrant the use of IORT as part of the management of biliary tract cancer.


Subject(s)
Adenocarcinoma/radiotherapy , Biliary Tract Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Acute Disease , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Aged , Biliary Tract Neoplasms/mortality , Biliary Tract Neoplasms/surgery , Cholangitis/complications , Chronic Disease , Combined Modality Therapy , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Intraoperative Period , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Pilot Projects , Radiation Injuries/etiology , Radiotherapy Dosage , Retrospective Studies , Severity of Illness Index
20.
AJR Am J Roentgenol ; 145(4): 833-7, 1985 Oct.
Article in English | MEDLINE | ID: mdl-3876008

ABSTRACT

The accuracy of physical examination is compared with that of computed tomography (CT) of the chest in determining the extent of disease in 42 patients with local and/or regional recurrence of breast cancer. Of the 33 patients with clinical evidence of chest wall recurrence, 16 (49%) had areas of disease visible by CT that were clinically unsuspected. Similarly, in the nine patients who presented with supraclavicular and/or axillary recurrence, five (56%) had additional sites of involvement discovered on CT. Since many of these patients are treated with radiotherapy, the information gained by CT of the chest can be of great value in treatment planning.


Subject(s)
Breast Neoplasms/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Tomography, X-Ray Computed , Female , Humans , Lymphatic Diseases/diagnostic imaging , Palpation , Physical Examination
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