Martina Baur

Docetaxel/cisplatin as first-line chemotherapy in patients with head and neck carcinoma: a phase II trial.

The objective of this Phase II study was to assess the clinical activity and toxicity of docetaxel (D) and cisplatin (P) in patients with locally advanced unresectable, metastatic, or recurrent squamous cell carcinoma of the head and neck (SCCHN).

Extravasation of Oxaliplatin (Eloxatin®) – Clinical Course

Background: Up to now the cytostatic oxaliplatin was classified as nonvesicant. This is the first report on tissue necrosis induced by oxaliplatin extravasation in literature. A clinical course following oxaliplatin extravasation is reported. Case Report: A 52-year-old white female with adenocarcinoma of the colon and hepatic and pulmonary metastases received palliative chemotherapy consisting of oxaliplatin, leucovorin, and 5-fluorouracil. By mistake oxaliplatin infusion extravasated subcutaneously in the left forearm; consequently, a painless red swelling occurred without any sign of further damage of the tissue. The infusion cannula was removed and oxaliplatin was infused into the right median cubital vein at the elbow. Again oxaliplatin extravasated subcutaneously. A severe painful necrotic reaction of the underlying flexor muscles of the right elbow developed, disabling the patient for 2 months, showing red-brown painful swelling, sclerosis of the skin, induration, fixation, and immobilization of the right elbow. Nonsteroidal analgesics and antibiotics were given, and lymphatic drainage and physiotherapy performed as generally accepted polypragmatic unspecific therapeutic procedure. After 2 months, the patient was able to bow and extend the right elbow except for an extension deficit of 20°, pro- and supination became possible again, pain had completely resolved and strength recovered without limitation. Sclerosis of the skin and stiffness of the underlying tissue were slowly subsiding. Conclusion: Oxaliplatin can induce severe necrosis of underlying muscles by extravasation and therefore must be considered as a vesicant. Therefore oxaliplatin should be applied via a central venous access.

Intermittent hepatic portal vein gas complicating diverticulitis - A case report and literature review

Case reportThis report describes a case of intermittent hepatic portal venous gas (HPVG) because of colonic diverticulitis in a 48-year-old man, who was successfully treated by surgery.ConclusionBased on an extensive literature search, which produced 21 observations, the etiology, symptoms, imaging features, clinical significance, treatment strategy, and outcome of HPVG because of colonic diverticulitis are evaluated: While observations with an underlying intramesocolic abscess carry a favorable prognosis, the prognosis of observations because of septic thrombophlebitis with gas forming germs is poor.

Goserelin a GnRH‐analogue as third‐line therapy of refractory epithelial ovarian cancer

Between October 1988 and March 1991, 23 ovarian cancer patients with progressive disease whilst receiving second- or third-line polychemotherapy received subcutaneously 3.6 mg Goserelin, a GnRH analogue, at monthly intervals until further tumor progression. Four patients (17.4%) achieved partial response, 7 patients (30.4%) had stable disease and 12 patients (52.2%) showed further tumor progression. Median time to tumor progression was 8.5, 5.3 and 2.1 months, respectively (Mantel test, P = 0.0003). Ten out of 11 patients who showed partial response or no change had grade 2 or grade 3 tumors. We conclude that Goserelin shows evidence of antitumor activity also in grade 2 and grade 3 ovarian carcinoma. It offers a therapeutic alternative to a group of patients, in whom we usually terminate cytotoxic treatment.

Frequent MGMT (06-methylguanine-DNA methyltransferase) hypermethylation in long-term survivors of glioblastoma: a single institution experience

Frequent MGMT (06-methylguanine-DNA methyltransferase) hypermethylation in long-term survivors of glioblastoma: a single institution experience Background. The aim of this retrospective study was to analyse the MGMT (06-methylguanine-DNA methyltransferase) promoter methylation status in long-term surviving (≥ 3 years) patients with glioblastoma multiforme (GBM). Methods. The methylation status of the MGMT promoter was determined by bisulfite modification of the DNA and subsequent methylation-specific polymerase-chain-reaction (MSP). DNA was extracted from routinely formalin-fixed and paraffin-embedded tumour tissue samples. Results. MSP yielded interpretable results in only 14 of 33 (42%) long-term surviving patients with GBM. A methylated band was seen in 3 of 14, methylated as well as unmethylated bands in 8 of 14 and an only unmethylated band in 3 of 14 patients, thus, yielding MGMT promoter methylation in 11 of 14 patients. The two groups of patients with methylated and unmethylated MGMT promoter status were too small to draw any firm statistical conclusions. Conclusions. Long-term surviving patients with GBM have very frequently intratumoural MGMT promoter methylation. This phenomenon discriminates long-term survivors from a non-selected group of patients with GBM. The standardization of the MSP for the determination of the MGMT promoter methylation status seems to be necessary in order to make this methodology a more reliable one.

Ifosfamide/Mesna as Salvage Therapy in Platinum Pretreated Ovarian Cancer Patients—Long-Term Results of a Phase II Study

Purpose: Salvage chemotherapy in advanced ovarian cancer is not yet standardized. Patients: Twenty-one consecutive patients progressing on or relapsing after previous platinum-containing treatment were eligible for treatment with ifosfamide 5 g/m2 infused over a 24-hour period every 3 weeks in a Phase II trial. After an initial bolus of 1 g/m2 of mesna, mesna was applied at a dosage of 5 g/m2 concomitantly with ifosfamide followed by additional dosages of 200 mg 3 times at 4-hour intervals after termination of the ifosfamide infusion. Results: The rate of objective responses was 19 percent, with a 95%CI [5.45–41.91 percent]. One patient achieved a pathologic complete remission (pCR) and 3 patients a clinical partial remission (PR). Median time-to-progression was 3 months. One patient was a long-term survivor. Main toxicities according to NCI-CTC included Grade 4 neurotoxicity in one patient, Grade 3 gastrointestinal toxicity in 5 patients, Grade 3 infection in one patient, and Grade 3 and 4 leucopenia in 6 and 2 patients, respectively. Conclusions: Monotherapy with ifosfamide represents an active regimen for salvage chemotherapy in advanced ovarian cancer patients progressing on or relapsing after previous platinum-pretreatment, even yielding a long-term surivor.

Acute Reversible Heart Failure Caused by Coronary Vasoconstriction due to Continuous 5-Fluorouracil Combination Chemotherapy.

We present the case of a 51-year-old male patient who received adjuvant chemotherapy consisting of oxaliplatin, bolus and continuous 5-fluorouracil (5-FU) and leucovorin after anterior resection because of locally advanced rectal cancer. Preoperative chemotherapy with capecitabine (an oral 5-FU prodrug) had been well tolerated. Two days after initiation of the first course of chemotherapy, the patient reported typical chest pain. The ECG showed ST elevations and prominent T waves in almost all leads. Due to suspicion of a high-risk acute coronary syndrome, an urgent cardiac catheterization was performed. It showed a generally reduced coronary flow with multiple significant stenoses (including the ostia of the left and right coronary artery), as well as a highly reduced left ventricular function with diffuse hypokinesia. Due to the meanwhile completely stable situation of the patient after medical acute coronary syndrome treatment, no ad hoc intervention was performed to allow further discussion of the optimal management. Thereafter, the patient remained clinically asymptomatic, without any rise in cardiac necrosis parameters; only NT-pro-BNP was significantly elevated. A control cardiac catheterization 2 days later revealed a restored normal coronary artery flow with only coronary calcifications without significant stenoses, as well as a normal left ventricular ejection fraction. Cardiovascular symptoms occurred on the second day of continuous 5-FU treatment. As cardiotoxic effects seem to appear more frequently under continuous application of 5-FU, compared to the earlier established 5-FU bolus regimens, treating medical oncologists should pay special attention to occurring cardiac symptoms and immediately interrupt 5-FU chemotherapy and start a cardiologic work-up.

Phase I/II study of oral etoposide plus GM-CSF as second-line chemotherapy in platinum-pretreated patients with advanced ovarian cancer

The aim of this phase I/II study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities of chronic oral etoposide given on days 1–10 followed by rescue with subcutaneous (s.c.) granulocyte-macrophage colony-stimulating factor (GM-CSF) on days 12–19 as second-line chemotherapy in platinum-pretreated patients (pts) with advanced ovarian carcinoma. Cohorts of three to six pts were treated with doses of oral etoposide from 750 mg m−2 cycle−1 escalated to 1250 mg m−2 cycle−1 over 10 days, every 3 weeks. Subcutanous GM-CSF, 400 μg once daily, days 12–19, was added if dose-limiting granulocytopenia was encountered. In total, 18 pts with a median Karnofsky index of 80% (range, 70–100%) and a median time elapsed since the last platinum dose of 10 months (range, 1–24 months), 30% of whom showed visceral metastases, were treated at four dose levels (DLs) of oral etoposide on days 1–10 of each cycle as follows: DL 1, 750 mg m−2 cycle−1, without GM-CSF, three pts; DL 2, 1000 mg m−2 cycle−1, without GM-CSF, three pts; DL 3, 1000 mg m−2 cycle−1, with GM-CSF, six pts; and DL 4, 1250 mg m−2 cycle−1, with GM-CSF, six pts. All pts were assessable for toxicity and 16 pts for response. Dose-limiting toxicity (DLT) was reached at DL 4 by three of six pts, showing World Health Organization (WHO) toxicity grade 4. One patient died from gram-negative sepsis associated with granulocytopenia grade 4. Two more pts developed uncomplicated granulocytopenia grade 4. Thus, we recommend that DL 3 can be used for further phase II evaluation (i.e. oral etoposide 1000 mg m−2 cycle−1, days 1–10, followed by s.c. GM-CSF 400 μg, days 12–19). The clinical complete or partial responses in each patient cohort were: DL 1, one of three pts; DL 2, one of three pts; DL 3, three of five pts; and DL 4, two of five pts. In conclusion, in this phase I/II study, we defined the MTD and the dose recommended for the therapy with oral etoposide given over 10 days followed by s.c. GM-CSF in platinum-pretreated patients with advanced ovarian cancer. Our data demonstrate encouraging activity of this regimen and strongly support its further investigation in a phase II study.

In vitro and in vivo evaluation of the combination of cisplatin and its analogue carboplatin for platinum dose intensification in ovarian carcinoma

Background. Cisplatin and its analogue carboplatin have been shown to cause dose‐dependent growth inhibition throughout a wide dose range in the ovarian cancer cell lines OVCAR‐3, 2780, HTB‐77, and CRL‐1572 tested. Cisplatin was 30 times more effective than carboplatin. The combination of both substances led to a less‐than‐synergistic effect, as was revealed by an isobologram in the OVCAR‐3 cell line. Because of the different toxicity pattern, cisplatin and carboplatin theoretically are ideal candidates for combination chemotherapy in platinum‐sensitive tumors.

High dose single-agent paclitaxel in a hemodialysis patient with advanced ovarian cancer: a case report with pharmacokinetic analysis and review of the literature

There exists only scarce data on the pharmacokinetics of paclitaxel in patients with renal insufficiency. A 53-year-old woman on hemodialysis was treated with paclitaxel for relapsed ovarian cancer. Paclitaxel was administered as a 3-h infusion at 175, 225, and 300 mg/m2 on nonhemodialysis days. The pharmacokinetic analysis revealed independence of the pharmacokinetic parameters for paclitaxel from the extent of renal (dys-)function. The peak plasma concentration of the 300 mg/m2 dose level before and after dialysis was 23.05 and 21.01 ng/mL, respectively, proving that paclitaxel was not dialysable. The area under the plasma concentration versus time curve for the standard and highest dose of paclitaxel was 12,200 ng·h/mL in mean and 40,936 ng·h/mL, respectively. The absence of marked side effects at all dose levels was in line with the independence of the pharmacokinetic parameters for paclitaxel from renal function. No objective response was found, but a marked improvement of symptoms from gastrointestinal obstruction as well as a decrease in the serum CA125 level were observed. Patients with terminal renal failure undergoing hemodialysis tolerate conventional and even high doses of paclitaxel without experiencing severe toxicity.